2. Key Areas Determining Sensory Level
3. Key Muscles Determining Motor Level
4. Grading of Muscle Strength
5. Grading of Deep Tendon Reflexes
6. Testing of Cranial Nerves
B. Epilepsy
1. Partial (Focal Epilepsy)
Characterized by focal cortical discharges that provoke seizure sx related to the area of the brain involved. Simple partial seizures do not cause impaired consciousness, whereas complex partial seizures involve an alteration in consciousness.
Etiology
Temporal lobe epilepsy (most common form epilepsy in adults) manifests as a complex partial seizure.
Frequent causes of partial seizures are tumor, stroke, CNS infections (cysticercosis, abscesses), AVMs, traumatic brain injury, cortical malformations, and idiopathic/genetic conditions.Diagnosis
EEG
Ambulatory EEG and/or video EEG if diagnostic uncertaintyH&P
Usually physical/neurologic exam is nl unless the cause is structural abnlity (stroke), wherein neuro exam is consistent with the area of CNS structural damage.
During partial seizures pts are conscious, unless there is spread of the epileptic focus causing secondary generalization and unresponsiveness. A focal seizure can evolve to a generalized tonic clonic seizure. Table 10-4 describes clinical manifestations of different types of focal seizures and areas of the brain involved.Imaging
Head CT to r/o space-occupying lesions. If possible, avoid in children unless an emergency.
Brain MRI with defined epilepsy protocol should be performed if recurrent seizures.Treatment
First unprovoked seizure with nl imaging/EEG/labs generally requires no Rx; recurrent or abnl w/up requires Rx with compliance; avoidance of EtOH and sleep deprivation is essential to prevent recurrence.
No driving is allowed until seizure freedom in accordance w/local laws/regulations (47% seizure free w/monoRx, 67% w/polyRx).
Avoid valproic acid (↑ risk teratogenicity) in women of childbearing age and regardless of antiepileptic drug taken; begin folic acid (1-4 mg/day) to prevent neural tube defects.
Carbamazepine is the traditional initial drug for partial seizures.
FIGURE 10-1 Spinal dermatomes. (From Green GM [ed]: The Harriet Lane Handbook: A Manual for Pediatric House Officers, 12th ed. St. Louis, Mosby–Year Book, 1991.)
TABLE 10-1
Grading of Muscle Strength
| Grade | Description |
| 0 | Absent muscle contraction |
| 1 | Minimal contraction |
| 2 | Active movement with gravity eliminated |
| 3 | Active movement against gravity only |
| 4 | Active movement against gravity and some resistance |
| 5 | Normal muscle strength |
TABLE 10-2
Grading of Deep Tendon Reflexes
| Grade | Description |
| 0 | Absent |
| + | Hypoactive |
| ++ | Normal |
| +++ | Brisker than average |
| ++++ | Hyperactive, often indicative of disease |
TABLE 10-3
Testing of Cranial Nerves
| Cranial Nerves | Action | |
| I | Olfactory | Sense of smell |
| II | Optic | Vision (visual acuity, visual fields, color) |
| III | Oculomotor | Extraocular movement, pupillary constriction (oculomotor), elevation of upper lids, abduction of eye |
| IV | Trochlear | |
| VI | Abducens | |
| V | Trigeminal | Mastication; sensory of forehead, face, and jaw |
| VII | Facial | Facial expression; taste in anterior two thirds of tongue |
| VIII | Acoustic | Hearing and balance |
| IX | Glossopharyngeal | Sensory and motor functions of pharynx and larynx (gag reflex, position of uvula, swallowing) |
| X | Vagus | |
| XI | Accessory | Shrugging of shoulders, movement of head, motor to trapezius, sternocleidomastoid |
| XII | Hypoglossal | Motor control of tongue |
TABLE 10-4
Clinical Manifestations of Different Types of Focal Seizures and Areas of the Brain Involved
| Seizure Type | Areas of Brain Involved | Clinical Expression |
| Somatosensory | Postcentral rolandic; parietal | Contralateral intermittent or prolonged tingling, numbness, sense of movement, desire to move, heat, cold, electric shock; sensation may spread to other body segments |
| Parietal | Contralateral agnosia of a limb, phantom limb, distortion of size or position of body part | |
| Second sensory; supplementary sensory-motor | Ipsilateral or bilateral facial, truncal or limb tingling, numbness, or pain; often involving lips, tongue, fingertips, feet | |
| Motor | Precentral rolandic | Contralateral regional clonic jerking, usually rhythmic, may spread to other body segments in jacksonian motor march; often accompanied by sensory symptoms in same area |
| Supplementary sensory-motor | Bilateral tonic contraction of limbs causing postural changes; may exhibit classic fencing posture; may have speech arrest or vocalization | |
| Frontal | Contralateral head and eye version, salivation, speech arrest or vocalization; may be combined with other motor signs (as above) depending on seizure spread | |
| Auditory | Heschl’s gyrus—auditory cortex in superior temporal lobe | Bilateral or contralateral buzzing, drumming, single tones, muffled sounds |
| Olfactory | Orbitofrontal; mesial temporal cortex | Often described as unpleasant odor |
| Gustatory | Parietal; rolandic operculum; insula; temporal lobe | Often unpleasant taste, acidic, metallic, salty, sweet, smoky |
| Vertiginous | Occipitotemporal-parietal junction; frontal lobe | Sensation of body displacement in various directions |
| Visual | Occipital | Contralateral static, moving, or flashing colored or uncolored lights, shapes, or spots; contralateral or bilateral, partial or complete loss of vision |
| Temporal; occipitotemporal-parietal junction | Formed visual scenes, faces, people, objects, animals | |
| Limbic | Limbic structures: amygdala, hippocampus, cingulum, olfactory cortex, hypothalamus | Autonomic: abdominal rising sensation, nausea, borborygmi, flushing, pallor, piloerection, perspiration, heart rate changes, chest pain, shortness of breath, cephalic sensation, lightheadedness, genital sensation, orgasm Psychic: déjà vu, jamais vu, depersonalization, derealization, dreamlike state, forced memory or forced thinking, fear, elation, sadness, sexual pleasure; hallucinations or illusions of visual, auditory, or olfactory nature |
| Dyscognitive | Usually bilateral involvement of limbic structures (see above) | Previously known as “complex partial seizures,” characterized by a predominant alteration of consciousness or awareness; current definition requires involvement of at least two of five components of cognition: perception, attention, emotion, memory, and executive function |
From Goldman L, Schafer AI (eds): Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.
Box 10-1 Key Areas Determining Sensory Level
| C2 | Occipital protuberance | T6 | Sixth intercostal space, xiphisternum |
| C3 | Supraclavicular fossa | T7-9 | Intercostal spaces |
| C4 | Top of the acromioclavicular joint | T10 | Umbilicus |
| C5 | Lateral side of the antecubital fossa | T11 | Intercostal space |
| C6 | Thumb | T12 | Inguinal ligament |
| C7 | Middle finger | L1 | Upper anterior thigh |
| C8 | Little finger | L2 | Midanterior thigh |
| T1 | Medial side of the antecubital fossa | L3 | Medial femoral condyle |
| T2 | Apex of the axilla | L4 | Medial malleolus |
| T3 | Third intercostal space | L5 | Dorsum of the foot at the third metatarsophalangeal joint |
| T4 | Fourth intercostal space, nipple line | S1 | Lateral heel |
| T5 | Fifth intercostal space | S2 | Popliteal fossa in the midline |
| S3 | Ischial tuberosity | ||
| S4-5 | Perianal area |
Lamotrigine and levetiracetam are effective and well tolerated.
Antiepileptics (lacosamide, oxcarbazepine, ezogabine) may be used by epilepsy specialists.
Surgery (temporal lobectomy in mesial temporal sclerosis) may be indicated in refractory cases.2. Idiopathic General Epilepsy
Table 10-5 describes a classification and clinical expression of generalized seizures.
Diagnosis
EEG
Ambulatory EEG and/or video EEG if diagnostic uncertaintyTABLE 10-5
Generalized Seizures: Classification and Clinical Expression
| Seizure Type | Subtype | Clinical Expression |
| Absence | Typical | Abrupt cessation of activities, with motionless, blank stare and loss of awareness lasting ≈10 sec; the attack ends suddenly, and pt resumes normal activities immediately |
| Atypical | Longer duration than typical absence, often accompanied by myoclonic, tonic, atonic, and autonomic features as well as automatisms | |
| With myoclonias | Absence with myoclonic components of variable intensity | |
| Myoclonic | Myoclonic | Sudden, brief (<100 msec), shocklike, involuntary, single or multiple contractions of muscle groups of various locations |
| Myoclonic-atonic | A sequence consisting of a myoclonic followed by an atonic phase | |
| Myoclonic-tonic | A sequence consisting of a myoclonic followed by a tonic phase | |
| Tonic | Sustained increase in muscle contraction lasting a few seconds to minutes | |
| Clonic | Prolonged, regularly repetitive contractions involving the same muscle groups at a rate of 2-3 cycles/sec | |
| Atonic | Sudden loss or diminution of muscle tone lasting 1-2 sec, involving head, trunk, jaw, or limb musculature | |
| Tonic-clonic | A sequence consisting of a tonic followed by a clonic phase |
From Goldman L, Schafer AI (eds): Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.
Labs
Routine blood w/up (CBC, CMP, glucose, electrolytes), urine tox screen
LP recommended if suspicion of meningitisImaging
Head CT scan r/o space-occupying lesions; avoid in children unless a neurologic emergency
MRI of the brain epilepsy protocol performed in all pts with recurrent seizuresTreatment
First unprovoked seizure with nl imaging/EEG/laboratory w/up requires no Rx; recurrent seizures or pts w/abnl w/up require Rx based on type/etiology.
Chronic Rx is indicated for more than two unprovoked seizures or in pts with one seizure with abnl w/up.
Levetiracetam (initial dose 250-500 mg bid, max 1500 mg bid) is an effective and well-tolerated antiepileptic drug for generalized tonic clonic seizures.
Valproic acid (initial dose 10-15 mg/kg/day div bid, max dose 60 mg/kg/day) is better tolerated than topiramate and more efficacious than lamotrigine in pts w/generalized and unclassified epilepsy types; avoid valproic acid (↑ risk teratogenicity) in women of childbearing age and regardless of antiepileptic drug taken; begin folic acid (1-4 mg/day) to prevent neural tube defects.
No driving is allowed until seizure freedom in accordance with local laws and regulations.3. Status Epilepticus
Continuous seizure activity lasting ≥5 min or two or more discrete seizures w/incomplete recovery of consciousness between them.
Diagnosis
Convulsive status epilepticus: Pts are unresponsive w/obvious tonic, clonic, or tonic-clonic extremity movements.
Nonconvulsive status epilepticus varies from complete unresponsiveness w/little or no observable motor activity to confusion and/or repetitive behaviors/automatisms; confirm dx by video EEG monitoring or paradoxical improvement in ms after low-dose benzodiazepine.Management
C. Stroke
1. Transient Ischemic Attack (TIA)
Transient neurologic deficit resulting from focal brain, spinal cord, or retinal ischemia without acute infarction; sx typically <60 min with full function recovery. TIA is a neurologic emergency because 40% pts w/ischemic stroke experience a prior TIA.
FIGURE 10-2 Management algorithm for status epilepticus. CPSE, complex partial status epilepticus; GSCE, generalized convulsive status epilepticus, NCSE, nonconvulsive status epilepticus; SE, status epilepticus. (From Vincent JL, Abraham E, Moore FA, et al [eds]: Textbook of Critical Care, 6th ed. Philadelphia, Saunders, 2011.)
Box 10-3 Characteristics of Carotid Artery Syndrome
Ipsilateral monocular vision loss (amaurosis fugax); the pt often feels as if “a shade” has come down over one eye
Episodic contralateral arm, leg, and face paresis and paresthesias
Slurred speech and transient aphasia
Ipsilateral headache of vascular type
Carotid bruit may be present over the carotid bifurcation
Microemboli, hemorrhages, and exudates may be noted in the ipsilateral retina
Box 10-4 Characteristics of Vertebrobasilar Artery Syndrome
Binocular visual disturbances (blurred vision, diplopia, and total blindness)
Vertigo, N/V, and tinnitus
Sudden loss of postural tone of all four extremities (drop attacks) w/no loss of consciousness
Slurred speech, ataxia, and numbness around lips or face
Etiology
Cardioembolic
Large-vessel atherothrombotic disease
Lacunar disease
Hypoperfusion w/fixed arterial stenosis
Hypercoagulable statesDiagnosis
H&P
Imaging
Head CT, brain MRI, MRA
Carotid Doppler, echo, ECG
Telemetry for hospitalized ptsLabs
CBC w/Plt, PT, PTT
Glucose, lipid profile, ESR
CXR; other tests dictated by suspected etiologyTreatment
Depends on etiology. Table 10-6 describes the characteristics of thrombosis vs embolism. The ABCD2 score can help stratify pts who are at highest risk of subsequent stroke after TIA (Table 10-7). Consider hospital admission for pts with ABCD2 score >3 or those with transient monocular blindness.
Acute anticoagulation is indicated for new-onset AF and atherothrombotic carotid disease causing recurrent transient neurologic sx, especially before carotid endarterectomy (CEA) or carotid stenting. It is also considered for basilar artery thrombosis, given concern for progression to brainstem stroke w/high morbidity and mortality.
Antiplatelet therapy should be used to reduce the risk of recurrent TIAs or subsequent stroke. Three antiplatelet agents are commonly used in stroke prevention: aspirin, aspirin/dipyridamole, and clopidogrel. All are reasonable choices, but practitioners should consider their individual pt’s comorbidities when selecting an antiplatelet agent.
Chronic therapy should be aimed at modifying the four major risk factors: BP control, control of dyslipidemia, control of blood sugar, and smoking cessation.TABLE 10-6
Characteristics of Thrombosis and Embolism
| Thrombosis | Embolism | |
| Onset of sx | Progression of sx during hours to days | Very rapid (seconds) |
| Hx of previous TIA | Common | Uncommon |
| Time of presentation | Often during night hours while pt is sleeping Classically, pt awakens w/a slight neurologic deficit that gradually progresses in a stepwise fashion |
Pt is usually awake and involved in some type of activity |
| Predisposing factors | Atherosclerosis, HTN, diabetes, arteritis, vasculitis, hypotension, trauma to head and neck | AF, mitral stenosis and regurgitation, endocarditis, mitral valve prolapse |
TABLE 10-7
ABCD2 Risk of Stroke After a TIA
| Score (points) | |
| Age ≥60 yr | 1 |
| BP: ≥140 mm Hg systolic or 90 mm Hg diastolic | 1 |
| Clinical features Unilateral weakness Speech disturbance without weakness |
2 1 |
| Duration of TIA ≥60 min 10-59 min |
2 1 |
| Presence of diabetes mellitus | 1 |
| Two-day risk of stroke is 4.1% with a score 4-5 and 8.1% with a score 6-7. | |
Modified from Ballinger A: Kumar & Clark’s Essentials of Clinical Medicine, 6th ed. Edinburgh, Saunders, 2012.
2. Ischemic Stroke
Rapid onset of neurologic deficit involving a certain vascular territory secondary to thrombosis or embolism
Diagnosis
H&P
Imaging
Immediate CT of the head without contrast or MRI of the brain with stroke protocol to rule out hemorrhage and, if possible, to assess the extent of stroke. CT of brain: area of ↓ density; initial CT scan may be nl because the infarct may not be evident for 2 to 3 days afterward.
TABLE 10-8
Selected Stroke Syndromes
| Artery Involved | Neurologic Deficit |
| Middle cerebral artery | Hemiplegia (UEs and face usually more involved than LEs) Hemianesthesia (hemisensory loss) Hemianopia (homonymous) Aphasia (if dominant hemisphere is involved) |
| Anterior cerebral artery | Hemiplegia (LEs more involved than UEs and face) Primitive reflexes (e.g., grasp and suck) Urinary incontinence |
| Vertebral and basilar arteries | Ipsilateral cranial nerve findings, cerebellar findings Contralateral (or bilateral) sensory or motor deficits |
| Deep penetrating branches of major cerebral arteries (lacunar infarction) | Usually seen in elderly pts with HTN and diabetic pts Four characteristic syndromes are possible: 1. Pure motor hemiplegia (66%)
2. Dysarthria—clumsy hand syndrome (20%)
3. Pure sensory stroke (10%)
4. Ataxic hemiplegia syndrome w/pyramidal tract signs
|
Treatment
IV TPA is the only medical therapy approved by the U.S. FDA for the treatment of acute ischemic stroke.
The time window for administration is ≤3 hr of symptom onset.
The protocol is weight based, with 90 mg being the maximum allowable dose.
The risk of brain hemorrhage with IV TPA is ≈5% in pts w/stroke.
Multimodal therapy (i.e., thrombectomy and intra-arterial TPA) is sometimes performed.
Endovascular treatment may be performed for select cases in which IV TPA has failed to recanalize an occluded artery.
Endovascular intervention may be an option for pts w/systemic contraindications to IV TPA.Box 10-5 Inclusion and Exclusion Criteria for IV TPA
Inclusion Criteria
1. Ischemic stroke onset is within 3 hours of drug administration.
2. Measurable deficit is noted on NIH Stroke Scale examination.
3. Pt’s CT does not show hemorrhage or nonstroke cause of deficit.
4. Pt’s is >18 years old.
Exclusion Criteria (Absolute)
1. Pt’s symptoms are minor or rapidly improving.
2. Pt had seizure at onset of stroke.
3. Pt has had another stroke or serious head trauma within the past 3 months.
4. Pt had major surgery within the last 14 days.
5. Pt has known hx of intracranial hemorrhage.
6. Pt has sustained SBP >185 mm Hg.
7. Pt has sustained DBP >110 mm Hg.
8. Aggressive treatment is necessary to lower the pt’s BP.
9. Pt has symptoms suggestive of SAH.
10. Pt has had gastrointestinal or urinary tract hemorrhage within the last 21 days.
11. Pt has had arterial puncture at noncompressible site within the last 7 days.
12. Pt has received heparin with the last 48 hours and has elevated PTT.
13. Pt’s PT is >15 sec.
14. Pt’s Plt count is <100,000 μL.
15. Pt’s serum glucose is <50 or >400 mg/dL.
Exclusion Criteria (Relative)
1. Pt has a large stroke with NIH Stroke Scale score >22.
2. Pt’s CT shows evidence of large MCA territory infarction (i.e., sulcal effacement or blurring of gray-white junction in greater than one third of MCA territory).
NIH, National Institutes of Health.
Modified from Vincent JL, Abraham E, Moore FA, et al (eds): Textbook of Critical Care, 6th ed. Philadelphia, Saunders, 2011.
Endovascular intervention is useful only for large, accessible thrombi. Therefore, if a pt w/stroke is a candidate for IV TPA, then he or she should probably receive IV TPA.
Antiplatelet therapy: Beginning oral or feeding tube administration of aspirin (325 mg/day) ≤48 hours of stroke onset is advised. This will decrease the likelihood of a repeat ischemic stroke. Another oral antiplatelet regimen approved for secondary stroke prophylaxis (e.g., clopidogrel, aspirin plus extended-release dipyridamole) will also suffice and may be superior in the long term.
↑ BP is common during acute stroke, and it often subsides without specific Rx. In general, HTN is not treated acutely unless it is extremely high (e.g., >220 mm Hg SBP); unless there is evidence of organ damage caused by the HTN; or unless thrombolysis is being considered, in which case BP needs to ↓ (if it can be safely accomplished) to ∼185/110 mm Hg. It is risky to ↓ BP severely the presence of acute ischemic stroke. A 15% to 25% decrease over the first 24 hours is recommended.3. Acute Hemorrhagic Stroke
a. Intracranial hemorrhage
Neurologic deficit secondary to intracerebral hemorrhage (17% of all strokes)
Etiology
HTN (50%-60%)
Cerebral amyloid angiopathy (10%)
Hemorrhagic infarcts (10%)
Use of anticoagulants and fibrinolytic agents (10%)
Brain tumors (5%)
Vascular malformations (5%)Diagnosis
H&P
Signs of ↑ ICP (e.g., bradycardia, ↓ RR, third nerve palsy)
FIGURE 10-3 Circle of Willis. ACOM, anterior communicating artery; MCA, middle cerebral artery; PCA, posterior cerebral artery; PCOM, posterior communicating artery. (From Weissleder R, Wittenberg J, Harisinghani M, Chen JW [eds]: Primer of Diagnostic Imaging, 5th ed. St. Louis, Mosby, 2011.)
Imaging
Immediate: CT scanning of the head without contrast is highly sensitive for hemorrhage (area of hemorrhagic infarct appears as a zone of ↑ density).
MRI of the brain with a gradient echo sequence is also highly sensitive for hemorrhage, including intracerebral microhemorrhages that may not be visible with CT scanning.Treatment
Surgery should be performed promptly for cases of cerebellar hemorrhage of >3 cm when the pt is deteriorating clinically or showing brainstem edema or hydrocephalus.
Surgery for lobar or deep brain clots may be considered for select cases, although the level of evidence for efficacy is not high.
Pneumatic compression devices should be applied to help prevent DVT.
Early mobilization for rehabilitation is desirable.TABLE 10-9
Localizing Signs in Pts w/Intracerebral Hemorrhage
| Location of Intracerebral Hemorrhage | Common Neurologic Signs | Examples |
| Putamen | Both eyes deviating conjugately to the side of the lesion (away from hemiparesis) Pupils normal in size and reacting normally Contralateral hemiplegia present Hemisensory defect noted |
Left putaminal hemorrhage |
| Thalamus | Both eyes deviating downward and looking at the nose Impairment of vertical eye movements present Pupils small (≈2 mm) and nonreactive Contralateral hemisensory loss present |
Thalamic hemorrhage |
| Pons | Both eyes in midposition No doll’s-eye movements Pupils pinpoint but reactive (use magnifying glass) Coma common Flaccid quadriplegia noted |
Pontine hemorrhage |
| Cerebellum | Ipsilateral paresis of conjugate gaze (inability to look toward side of lesion) Pupils normal in size and reacting normally Inability to stand or to walk Vertigo and dysarthria present |
Cerebellar hemorrhage |
HTN: BP should be quickly lowered by 15% and then gradually and safely brought to the individual pt’s target range. In theory, this may diminish expansion of the hematoma. Recommended guidelines for Rx of HTN in pts w/spontaneous hemorrhage are described in Box 10-6.
Hyperglycemia: A high blood glucose level predicts a worse outcome. Markedly elevated glucose levels should be lowered to <300 mg/dL.
Seizures: If seizures occur, they should be treated aggressively, including with IV medications, if needed.
↑ ICP: This condition should be treated with a graded approach, which may include the elevation of the head of the bed, analgesia/sedation, hyperventilation, and osmotic therapy.
Antipyretics should be administered for cases that involve fever; in addition, the cause of the fever should be sought.
Protamine sulfate is used to treat cases of heparin-induced intracerebral hemorrhage.
Vitamin K is given for warfarin-associated intracerebral hemorrhage. In addition, recombinant factor VIIa and fresh frozen plasma are sometimes used.
Recommendations for thrombolytic-associated intracerebral hemorrhage treatment include the consideration of the infusion of Plts and cryoprecipitate.b. Subarachnoid Hemorrhage (SAH)
Diagnosis
H&P
Abrupt onset of severe occipital or generalized headache that radiates into the posterior neck region and is worsened by neck and head movements; often described as “the worst headache” of the pt’s life
Restlessness, vomiting, diminished level of consciousness, syncope
Focal neurologic signs usually are absent.
Level of consciousness varies from nl to deeply comatose.
Fever and nuchal rigidity are present or usually develop within 24 hr.
Fundi may show papilledema or retinal hemorrhage.
Cranial nerve abnlities may be noted (e.g., pupillary dilation secondary to oculomotor nerve dysfunction).
HTN may be present and can lead to an incorrect dx of primary hypertensive emergency.
Tachycardia and irregular heartbeat may be present (≤91% of pts w/SAH have cardiac arrhythmias).Imaging and Labs
CT of brain is (+) in >95% of cases, especially during the acute phase (i.e., 24-48 hr) after the onset of bleeding.
A CT angiogram or a cerebral angiogram is imperative for determining the origin of the SAH. Angiography may also be extremely useful because it may offer a therapeutic benefit via the coiling of the aneurysm.
Basic labs should include CBC, chemistry panel, PT, PTT, Plt count, troponin.
LP is a very important part of the w/up, especially because 3% of pts with normal CT scans show evidence of hemorrhage on LP. An RBC count of >100,000/m3 strongly suggests SAH. If RBC counts ↓ between the first and fourth tubes, then the tap is most likely traumatic. The presence of xanthochromia or bilirubin in the CSF is a sign of SAH.Treatment
Management of SAH varies w/the pt’s clinical status (Table 10-10), as well as the location (see Fig. 10-3) and surgical accessibility of the aneurysm.TABLE 10-10
Glasgow Coma Scale∗
| Eyes | Motor | Verbal |
| 1. None | 1. None | 1. None |
| 2. To pain | 2. Abnl extension | 2. Incomprehensible (groaning) |
| 3. To speech | 3. Abnl flexion | 3. Inappropriate |
| 4. Spontaneous | 4. Flexion (withdrawal) | 4. Disoriented, confused |
| 5. Localizing | 5. Oriented | |
| 6. Obeying commands |
∗ The best score for each response should be documented and communicated in the format described above. Assessment of the best motor score is based on the best response of the arms. For use in individual pts, separate description of the three components of the GCS is strongly recommended. For purposes of classification, the total GCS can be calculated by adding the best score obtained in each category. The GCS should be annotated to indicate confounding factors: T signifies an intubated pt; S, sedation; P, neuromuscular blockade.
From Vincent JL, Abraham E, Moore FA, et al (eds): Textbook of Critical Care, 6th ed. Philadelphia, Saunders, 2011.
Pts with a depressed level of consciousness may need to be intubated and mechanically ventilated in an ICU setting.
A lumbar drain or ventriculostomy is required should the pt develop hydrocephalus and ↑ ICP.
Initial management strategies are geared toward stabilizing the pt and preventing recurrent hemorrhage and hydrocephalus.
Tight BP control is paramount. This can be done with the use of drips (e.g., nitroprusside) or PRN medications. An SBP 120 to 150 mm Hg is recommended.
After an aneurysm has been identified, measures to secure it should be undertaken; this can be done by either clipping or coiling the aneurysm. Clipping consists of placing a clip around the neck of the aneurysm and is performed via intra-arterial angiography; it consists of deploying platinum coils inside the aneurysm to cause thrombosis of the aneurysmal sac.
Pain control is performed with the use of short-acting and less-sedating medications (e.g., codeine, low-dose morphine).
Seizures occur in ≤3% of pts during the acute phase; however, the use of prophylactic antiepileptics is still controversial.
Vasospasm, which typically begins around day 3 after the hemorrhage and reaches a peak on day 6 to 8, is the leading cause of death and disability after aneurysm rupture. Nimodipine has been shown to improve outcomes if it is administered between days 4 and 21 after the hemorrhage, even if it does not significantly reduce the amount of vasospasm detected on angiography. After vasospasm develops, “triple H” therapy—to achieve Hypertension, Hypervolemia, and Hemodilution—is used in an attempt to provide adequate cerebral perfusion.4. Sinus Venous Thrombosis
Etiology
Staphylococcus aureus (50%-60%), Streptococcus (second leading cause), gram(−) rods/anaerobes; sphenoid sinusitis (most common site)Diagnosis
H&P
Ptosis, proptosis
Chemosis
CN palsies (III, IV, V (VI and VII), VI); VI is most common
Sensory deficits of the ophthalmic/maxillary branch of the fifth nerve are common.Labs
CBC, ESR, blood/sinus cultures (identify infectious primary source)
LP necessary to r/o meningitisImaging
MRV, MRI w/gadolinium including MR angiographyTreatment
Rx should take into account the primary source of infection, as well as possible associated complications, such as brain abscess, meningitis, or subdural empyema.
Broad-spectrum IV abx are used as empiric Rx until a definite pathogen is found. Rx should include a penicillinase-resistant PCN at maximum dose plus a third- or fourth-generation ceph:• Nafcillin (or oxacillin) 2 g IV q4h plus either ceftriaxone (2 g q12h) or cefepime (2 g q6h)
• Metronidazole 500 mg IV q6h should be added if anaerobic bacterial infection is suspected (dental or sinus infection).
• Vancomycin (1 g q12h w/nl renal function) may be substituted for nafcillin if significant concern exists for infection by MRSA or resistant Streptococcus pneumoniae.
Anticoagulation w/heparin: controversial. Cerebral infarction or ICH should first be ruled out by non–contrast-enhanced CT scan before initiation of heparin Rx. Current recommendation is for early heparinization in pts w/unilateral CST to prevent clot propagation and to ↑ the incidence of septic emboli. Warfarin Rx should be avoided in the acute phase of the illness but should ultimately be instituted to achieve an INR of 2 to 3 and continued until the infection, sx, and signs of CST have resolved or significantly improved.
Steroid Rx: controversial but may prove helpful in ↓ cranial nerve dysfunction or when progression to pituitary insufficiency occurs. Corticosteroids should be instituted only after appropriate abx coverage. Dexamethasone 10 mg q6h is the Rx of choice.
Emergency surgical drainage w/sphenoidotomy: indicated if the primary site of infection is thought to be the sphenoid sinus.
All pts w/CST are usually treated w/prolonged courses (3-4 wk) of IV abx. If there is evidence of complications such as intracranial suppuration, 6 to 8 wk of total Rx may be warranted.
All pts should be monitored for signs of complicated infection, continued sepsis, or septic emboli while abx Rx is being administered.5. Stroke Prevention: Asymptomatic Carotid Stenosis
Carotid stenosis is narrowing of the arterial lumen within the carotid artery.
Etiology
Atherosclerosis (most common)
Aneurysm
Arteritis
Carotid dissection
Postradiation necrosis
Vasospasm
Risk factors: HTN, dyslipidemia, DM, and smokingDiagnosis
Carotid duplex. If carotid stenosis is suspected on carotid duplex, but results are inconclusive, MRI, CT angiography, or traditional angiography should be obtained to confirm the degree of stenosis.H&P
Pts with carotid stenosis are often asymptomatic, but many have presence of a carotid bruit or TIA.Treatment (Table 10-11)
CEA and carotid angioplasty and stenting are available.
CEA: The selection of surgical candidates should be guided primarily by the presence or absence of symptoms and the degree of stenosis.Asymptomatic Pts
CEA should be considered in asymptomatic pts only if the perioperative risk for stroke and death at the given surgical institution is <3%.
CEA should be considered in pts between the ages of 40 and 75 yr with an asymptomatic 60% to 99% stenosis if their life expectancy is >5 yr and the perioperative stroke and mortality rates are <3%. However, medical therapy has improved since early trials comparing medical management and revascularization, and many experts are favoring intensified medical management rather than revascularization procedures in pts with ACS.
All pts undergoing CEA should be started on aspirin (ASA 81 or 325 mg daily) before surgery, and aspirin should be continued indefinitely.Symptomatic Pts
CEA is recommended for recently symptomatic pts with 70% to 99% stenosis if their life expectancy is >5 yr and perioperative risk for mortality is <6%.
CEA is beneficial for recently symptomatic men with 50% to 69% stenosis if their life expectancy is >5 yr and perioperative risk of mortality is <6%. Medical management is recommended for pts with stenosis <50%.
General medical therapy should be aimed at risk factor reduction. Major risk factors for carotid stenosis are HTN, DM, lipid disorders, and smoking.
Antiplatelet therapy: Three antiplatelet options are available for pts with carotid stenosis: ASA, ASA plus dipyridamole, and clopidogrel.TABLE 10-11
Carotid Stenosis Management
| Degree of Carotid Stenosis | <50% | 50%-69% | 70%-99% |
| Asymptomatic | Medical management | Men: CEA if stenosis >60% and age <75 yr; otherwise, medical management Women: medical management |
Men <75 yr: CEA Women: medical management |
| Symptomatic | Medical management | Men: CEA Women: medical management |
Men: CEA Women: CEA |
From Ferri F: Ferri’s Clinical Advisor: 5 Books in 1. 2013 edition. Philadelphia, Mosby, 2012.
D. Headaches
Table 10-12 compares the various types of headache.
1. Migraine (Aura, Trigger)
Recurrent headaches are preceded by a focal neurologic sx (migraine w/aura), occur independently (migraine w/o aura), or have atypical presentations (migraine variants). Aura, typically w/visual or sensory sx, develops over 5 to 20 min. In both migraine w/and w/o aura, headache is typically unilateral, pulsatile, and associated with N/V, photophobia, and phonophobia.
Treatment
Acute Abortive Rx
Triptans (SC, PO, and intranasal) are the drug class of choice for abortive Rx.
Early administration improves effectiveness.Prophylactic Rx
Prophylactic Rx is generally indicated when headaches occur >once/wk or when symptomatic Rxs are contraindicated or not effective. All prophylaxis should be maintained for ≥3 mo before deeming the medication a failure.TABLE 10-12
Differential Diagnosis of Headache
| Headache Type | Genetics | Epidemiology | Characteristic Features | Length | Accompanying Symptoms |
| Migraine headache | Complex genetics but usually a fhx | More frequent in women | Unilateral, bilateral; throbbing; moderate to severe; worsens with activity | Hours to days | Photophobia, phonophobia, nausea and/or vomiting |
| Tension-type headache | Usually a fhx | Equally frequent in men and women | Tight bandlike pain; bilateral; pain may be mild to moderate; improves with activity | Hours to days | No nausea or vomiting; small amount of light or sound sensitivity, but not both |
| Cluster headache | Possibly a fhx | More frequent in men | Unilateral, severe pain in the face | Minutes to hour | Ipsilateral ptosis, miosis, rhinorrhea, eyelid edema, tearing |
| Paroxysmal hemicrania | Usually no fhx | More frequent in women | Unilateral pain in the face | Minutes | Ipsilateral ptosis, miosis, rhinorrhea, eyelid edema, tearing; responds to indomethacin |
| Hemicrania continua | No fhx | More frequent in women | Unilateral, continuous headache with episodic stabbing pains | Continuous | Ipsilateral autonomic features: ptosis, miosis, rhinorrhea, eyelid edema, tearing |
fhx = family history
From Goldman L, Schafer AI (eds): Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.
Options include β-blockers (propranolol, timolol, atenolol, metoprolol), tricyclic antidepressants (amitriptyline), and the antiepileptic drug valproic acid.
Less-established options include Ca2+ channel blockers, selective serotonin reuptake inhibitors, and the antiepileptic drugs gabapentin and topiramate. The FDA has approved injection of onabotulinum toxin A (Botox) for prevention of headaches in adult pts with chronic migraines (≥15 headache days/mo for ≥3 mo).2. Tension-Type Headache (Bilateral, Vice-Like)
Recurrent headaches lasting 30 min to 7 days w/o N/V and w/at least two of the following: pressing or tightening quality (nonthrobbing), mild or moderate intensity, bilateral, and not aggravated by routine physical activity
Treatment
Relaxation and cognitive-behavioral Rx (especially in adolescents and children), Schultz-type autogenic training (relaxation technique based on passive concentration and body awareness of specific sensations), transcutaneous electrical nerve stimulation, heatAcute General Treatment
Nonnarcotic analgesics with limited frequency to prevent drug-induced and/or rebound headacheChronic Treatment
Tricyclic antidepressants (amitriptyline 10-150 mg qhs) and SSRIs
Avoid narcotics, limit NSAIDs, consider indomethacin; if related to cervical muscle spasm, consider a trial of muscle relaxants (e.g., metaxalone [Skelaxin] 400- 800 mg tid).3. Cluster Headache (Unilateral, Lacrimation, Periorbital)
Attacks of severe, unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 min, occurring from once every other day to eight times/day. Attacks are associated w/one or more of the following, all of which are ipsilateral: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead/facial sweating, miosis, ptosis, and eyelid edema. Most pts are restless or agitated during an attack.
Treatment
Abortive Treatment
Inhalation of 100% O2 by face mask for 15 min often aborts an attack.
75% of users of triptans (sumatriptan, zolmitriptan) are pain free within 20 min.
Ergotamine (Cafergot), octreotide, intranasal lidocaine, or dihydroergotamine may abort an attack or prevent one if given just before a predictable episode.Prophylaxis Treatment
Various medications have been tried without great success, although good responses may be obtained in up to 50% of cases. Examples include:• Valproic acid: start at 500 mg/day
• Topiramate: up to 50 mg bid
• Verapamil: up to 480 mg/day as tolerated
4. Idiopathic Intracranial Hypertension (IIH; Pseudotumor Cerebri)
Syndrome of ↑ ICP w/o underlying hydrocephalus/mass lesion + nl CSF analysis
Diagnosis
H&P
Symptoms• Headaches: generalized, throbbing, slowly progressive, worse with straining maneuvers, worse in the morning
• Transient visual obscurations as a brief blurring of vision or scotomata lasting <30 sec; occur frequently with Valsalva maneuver and may be monocular
• Double vision: most often in the horizontal plane (because of pseudo–sixth nerve palsy)
• Pulsatile tinnitus: may be initial symptom
• Photopsia: lights, sparkles in the eyes
• Pain: mainly retro-orbital; pain may also be located in the shoulders or neck and may be present without a headache; may be associated with Lhermitte’s sign.
Signs• Papilledema: in virtually all cases; bilateral but may be asymmetric
• Sixth nerve palsy: in approximately 10% to 20% of pts
• Visual field defects: enlarged physiologic blind spot, constricted visual fields
• Loss of vision: end result of long-standing and untreated IIH
Labs
CSF analysis: ↑ opening pressure, nl protein, glucose, and cell count
Hypercoagulability w/up if suspicion of venous sinus thrombosisImaging
Brain MRI r/o underlying structural lesions; empty sella sign often associated w/IIH but not pathognomonic
Cerebral venography/MRV to evaluate venous flow
CT (slit-like ventricles)Treatment
Weight loss in obese pts
CPAP if obstructive sleep apnea suspected
Acetazolamide 250 mg to 4 g/day: ↓ CSF production occurs by inhibition of carbonic anhydrase, occasionally causing anorexia and resultant weight loss.
Furosemide 40 to 120 mg/day in divided doses: Apparent mechanism of action is by ↓ Na+ transport, leading to ↓ total CSF volume.
Topiramate 100 to 400 mg/day: This antiepileptic medication, reported to be effective in Rx of IIH, is a weak carbonic anhydrase inhibitor with weight loss as one of its primary side effects.
Serial LP is attempted in pts with severe headaches resistant to medical Rx. Goal is to ↓ spinal fluid pressure, thus allowing immediate reduction in headache severity. This Rx should be reserved only for the most resistant cases and should be used as a conduit to future surgical intervention.
Surgical intervention is indicated in cases of Rx failure and progressive visual loss.
Optic nerve fenestration is preferred for pts with visual loss and easily controlled headaches.
E. Movement Disorders
1. Parkinson’s Disease (PD)
Progressive neurodegenerative disorder characterized clinically by rigidity, tremor, and bradykinesia and pathologically by cytoplasmic eosinophilic inclusions (Lewy bodies) in neurons of the substantia nigra and locus ceruleus and by depigmentation of the brainstem nuclei
Diagnosis
The four cardinal signs used to diagnose PD are (mnemonic = TRAP):• Tremor (resting, typically 4-6Hz)
• Rigidity, of the cogwheel type
• Bradykinesia/akinesia: slowness of movement
• Postural instability: failure of postural “righting” reflexes leading to poor balance and falls
One need not show all four cardinal signs to make a presumptive diagnosis of PD and begin treatment.Imaging
MRI of the head may sometimes distinguish between idiopathic PD and other conditions that manifest with signs of parkinsonism.Treatment
Physical therapy, pt education and reassurance, treatment of associated conditions (e.g., depression)
Avoidance of drugs that can induce or worsen parkinsonism: neuroleptics (especially high potency), certain antiemetics (prochlorperazine, trimethobenzamide), metoclopramide, nonselective MAO inhibitors (may induce hypertensive crisis), reserpine, methyldopaMedical Treatment
Whether levodopa or dopamine agonists should be the initial treatment remains controversial. In younger pts, agonists are usually the drug of choice; in pts >70 yr, levodopa is typically the drug of choice.
Levodopa is the cornerstone of symptomatic therapy. It should be used with a peripheral dopa decarboxylase inhibitor (carbidopa) to minimize side effects (nausea, lightheadedness, postural hypotension). The combination of the two drugs is marketed under the trade name Sinemet. Levodopa therapy has been found to reduce morbidity and mortality in pts w/PD.
Dopamine receptor agonists (Ropinirole and Pramipexole) are not as potent as levodopa, but they are often used as initial treatment in younger pts to attempt to delay the onset of complications (dyskinesias, motor fluctuations) associated with levodopa therapy. In general these drugs cause more side effects than levodopa, including nausea, vomiting, lightheadedness, peripheral edema, confusion, and somnolence. They can also cause impulse control behaviors such as hypersexuality, binge eating, and compulsive shopping and gambling. Presence of these behaviors must be assessed at each visit.
MAO-B inhibitors (rasagiline, selegiline, amantadine) can be used as monotherapy early in the disease or as adjunctive therapy in later stages. They have milder symptomatic benefit than dopamine agonists or levodopa and are well tolerated and easy to titrate. Concurrent use of stimulants and sympathomimetics should be avoided. Certain food restrictions may apply.
Anticholinergic agents (trihexyphenidyl, benztropine) are helpful only in treating tremor and drooling in pts w/PD. Potential side effects include constipation, urinary retention, memory impairment, and hallucinations. These drugs should be avoided in elderly pts.Surgical Options
Pallidal (globus pallidus interna) and subthalamic deep brain stimulation (DBS; subthalamic nucleus) are currently the surgical options of choice for pts w/advanced PD; similar improvement in motor function and adverse effects have been reported after either procedure. Compared with ablative procedures, DBS has the advantage of being reversible and adjustable. Thalamic DBS may be useful for refractory tremor. It improves the cardinal motor symptoms, extends medication “on” time, and reduces motor fluctuations during the day. In general pts are likely to benefit from this therapy if they show a clear response to levodopa. Therefore, when considering DBS, pts should be evaluated for motor response to levodopa by stopping levodopa overnight and evaluating motor response before and after a dose of levodopa.
Surgery is limited to patients with disabling, medically refractory problems, and pts must still have a good response to L-dopa to undergo surgery. DBS results in decreased dyskinesias, fluctuations, rigidity, and tremor.2. Ataxia
Vertebral-basilar artery ischemia
AIDS
Diabetic neuropathy
Vitamin B12 deficiency
MS and other demyelinating diseases
Meningomyelopathy
Cerebellar neoplasms, hemorrhage, abscess, infarct
Nutritional (Wernicke’s encephalopathy)
Paraneoplastic syndromes
Parainfectious: GBS, acute ataxia of childhood and young adults
Toxins: phenytoin, alcohol, sedatives, organophosphates
Wilson’s disease (hepatolenticular degeneration)
Hypothyroidism
Myopathy
Cerebellar and spinocerebellar degeneration: ataxia-telangiectasia, Friedreich’s ataxia
Frontal lobe lesions: tumors, thrombosis of anterior cerebral artery, hydrocephalus
Labyrinthine destruction: neoplasm, injury, inflammation, compression
Hysteria
Tabes dorsalis3. Essential Tremor
Predominantly postural and action tremor that is bilateral and tends to progress slowly during the years in the absence of other neurologic abnlities; most common of all movement disorders
Etiology
Often inherited (autosomal dominant); sporadic cases w/o an fhx also encounteredDiagnosis
Pts complain of tremor that is most bothersome when writing or holding something, such as a newspaper, or trying to drink from a cup. It worsens under emotional duress and is made better w/alcohol ingestion.
Tremor, 4 to 12 Hz, bilateral postural and action tremor of the UEs; may also affect the head, voice, trunk, and legs. Table 10-13 compares essential tremor with cerebellar and parkinsonian tremor.TABLE 10-13
Distinguishing Features of Parkinsonian, Cerebellar, and Essential Tremor
| Feature | Parkinson’s Syndrome | Cerebellar Tremor | Essential Tremor |
| Present at rest | Yes | No | Yes |
| Increased tone | Yes | No | No |
| Decreased tone | No | Yes | No |
| Postural abnlity | Yes | Yes | No |
| Head involvement | Yes | Yes | Yes |
| Intentional component | No | Yes | Yes |
| Incoordination | No | Yes | No |
From Remmel KS, Bunyan R, Brunback R, et al: Handbook of Symptom-Oriented Neurology, 3rd ed. St. Louis, Mosby, 2002.
Treatment
Propranolol
Primidone4. Dystonia
A group of disorders characterized by involuntary muscle contractions (sustained or spasmodic) that lead to abnl body movements or postures. It can be generalized or focal, of early (<20 yr) or late onset, and primary or secondary.
Etiology
Primary dystonia is believed to involve ↓/abnl basal ganglia activity resulting in disinhibition of motor thalamus and cortex, thus producing abnl movement.
Secondary dystonia results from CNS disease of basal ganglia (stroke, demyelination, hypoxia, trauma, Huntington’s disease, Wilson’s disease, Parkinson’s syndromes, and lysosomal storage diseases).
Acute dystonia is caused by drugs that block dopamine receptors.
TD can result from long-term Rx with antiemetics (e.g., phenothiazines), antipsychotics (e.g., haloperidol), levodopa, anticonvulsants, or ergots.Diagnosis
Hx (family hx, birth hx, trauma, medication use)
Physical examinationH&P
Focal dystonias• Neck (torticollis): most commonly affected site with a tendency for the head to turn to one side
• Eyelids (blepharospasm): involuntary closure of the eyelids that leads to excessive eye blinking, sometimes with persistent eye closure and functional blindness
• Mouth (oromandibular dystonia): involuntary contraction of muscles of the mouth, tongue, or face
• Hand (writer’s cramp)
• Isolated foot dystonia is very rare and may suggest an underlying parkinsonian disorder or brain structural abnlity.
Generalized dystonia• Affects multiple areas of the body and can lead to marked joint deformities
Labs
Usually not helpful for dx
Serum ceruloplasmin if Wilson’s disease is suspectedImaging
Primary dystonias are generally not associated with structural CNS abnormalities. CT scan or MRI of brain is indicated if a CNS lesion is suspected as a cause of secondary dystonia.
Electrophysiologic testing can provide support for the dx.Treatment
Acute Treatment
For acute dystonic reactions to phenothiazines/butyrophenones, use diphenhydramine 50 mg IV or benztropine 2 mg IV.Chronic Treatment
Pharmacologic Rx is often ineffective.
Slowly withdraw offending agents.
Diazepam, baclofen, or carbamazepine may be helpful.
Intrathecal baclofen is most useful for spastic or truncal dystonia.
Trihexyphenidyl or benztropine may be helpful in up to 50% of tardive dystonias.
For generalized dystonia, a trial of carbidopa/levodopa may be beneficial and diagnostic of dopa-responsive dystonia (DYT5).
Injection of botulinum toxin into the affected muscles is the standard Rx.
Surgical procedures, including denervation, myectomy, rhizotomy, thalamotomy (pallidotomy), or functional stereotactic surgery, may be helpful for severe, refractory cases.
DBS is becoming more promising, especially for refractory primary generalized dystonias.5. Chorea
Etiology
Pathology to the basal ganglia resulting in a pattern of discrete, randomly occurring jerks or twitches, either generalized or confined to a single body part
The most common type of chorea is dyskinesia produced by dopamine drugs in pts with PD.
The most common neurodegenerative choreic disorder is Huntington’s disease.Treatment
Severity ↓ by dopamine-depleting or D2 receptor-blocking agents6. Tardive Dyskinesia (TD)
Syndrome of involuntary movements associated with the long-term use of antipsychotic medication, particularly first-generation antipsychotics. Pts exhibit rapid, repetitive, stereotypic movements that mostly involve the oral, lingual, trunk, and limb areas.
Treatment
Clozapine has the best evidence for improving the sx of TD, although olanzapine and amisulpride may also be of benefit.7. Myoclonus
Sudden, brief, jerky, “shock-like” involuntary movements that can involve the muscles of the extremities, face, or trunk. (+) Myoclonus is caused by muscle contraction, whereas (−) myoclonus is caused by inhibition of active (such as postural) muscles. Myoclonus is a symptom that can be seen in a number of different neurologic disorders.
Treatment
Carefully remove or ↓ potentially causative medications.
For acute Rx of epileptic myoclonus, antiepileptic drugs such as valproic acid, levetiracetam, or clonazepam are helpful.
Clonazepam, valproic acid, levetiracetam are typically used for all forms of myoclonus, and often combinations of several medications seem to be more effective.8. Tourette’s Syndrome
Inherited neuropsychiatric disorder characterized by multiple motor and vocal tics that change during the course of the illness. Onset is typically before age 18 yr (new-onset tics can occasionally occur after age 18 yr, but for DSM-IV criteria of TS, they must begin before this age). Tics are sudden, brief, intermittent involuntary or semivoluntary movements (motor tics) or sounds (phonic or vocal tics) that mimic fragments of nl behavior.
Treatment
Dopamine-blocking agents may be used to ↓ severity of tics acutely (e.g., haloperidol 0.25 mg PO qhs initially). There are risks of side effects, such as acute dystonic reactions.
Clonidine: Many choose this as a first-line agent because of fewer long-term side effects. Start at 0.05 mg and slowly titrate to approximately 0.45 mg daily (needs tid/qid dosing). May also help with sx of ADHD.
Greater improvement in symptom severity among children with Tourette’s syndrome and chronic tic disorder has been reported with a comprehensive behavioral intervention compared with supportive Rx and education.
Important components of Rx are appropriate evaluation and Rx of coexisting conditions (e.g., ADHD, OCD).
DBS has shown some promising results as an alternative Rx in some pts with medically refractory disease.9. Wilson’s Disease
Wilson’s disease is a disorder of copper transport with inadequate biliary copper excretion, leading to an accumulation of the metal in liver, brain, kidneys, and corneas. The gene for Wilson’s disease is located on chromosome 13.
Diagnosis
H&P
Chronic liver disease/cirrhosis with hepatosplenomegaly, ascites, ↓ serum alb, prolonged prothrombin time, portal HTN
Neurologic presentation• Movement disorder: tremors, ataxia
Ocular: The Kayser-Fleischer ring is a gold-yellow ring seen at the periphery of the iris; these should be sought with slit-lamp examination by a skilled examiner.
Stigmata of acute or chronic liver diseaseLabs
↓ Serum ceruloplasmin level (<200 mg/L)
↓ Serum copper (<65 μg/L)
24-hr urinary copper excretion > 100 μg (nl <30 μg) to support dx; ↑ to > 1200 μg/24 hr after 500 mg of D-penicillamine (nl <500 μg/24 hr)
Liver bx (to confirm bx): hepatic copper content (>250 μg/g of dry weight) (nl is 20-50 μg)Treatment
10. Restless Legs Syndrome (RLS)
Autosomal dominant disorder common among first-degree relatives that manifests as an awake phenomenon consisting of an urge to move legs, usually associated with feeling of discomfort in legs
Classification
Primary RLS is without any obvious cause, with no associated disorder.
Secondary RLS is associated with other medical conditions. The most common associations are pregnancy, iron deficiency anemia, ESRD, and PD.Diagnosis
Polysomnography to document periodic limb movements during sleepLabs
Iron status: serum ferritin, total iron binding capacity, percent saturation
CBC for anemia, in case of iron deficiency
Metabolic panel: BUN and serum Cr for renal insufficiencyTreatment
Rx options for RLS• Dopamine agonists, pramipexole and ropinirole, are first-line agents.
• Anticonvulsants: Gabapentin was shown to be effective in multiple studies.
F. Dementia
Dementia is a syndrome characterized by progressive loss of previously acquired cognitive skills including memory, language, insight, and judgment. Alzheimer’s disease is believed to account for the majority (50% to 75%) of all cases of dementia.
Diagnosis
There is no definitive imaging or lab test for the dx of Alzheimer’s disease and most forms of dementia; rather, dx depends on clinical history, a thorough physical and neurologic exam, and use of reliable and valid diagnostic criteria (i.e., DSM-V or NINDCS-ADRDA) such as the following:• Loss of memory and one or more additional cognitive abilities (aphasia, apraxia, agnosia, or other disturbance in executive functioning)
• Impairment in social or occupational functioning that represents a decline from a previous level of functioning and results in significant disability
• Deficits that do not occur exclusively during the course of delirium
• Insidious onset and gradual progression of symptoms
• Cognitive loss documented by neuropsychologic tests
• No physical signs, neuroimaging, or laboratory evidence of other diseases that can cause dementia (i.e., metabolic abnlities, medication or toxin effects, infection, stroke, PD, subdural hematoma, or tumors)
H&P
Spouse or other family member, usually not the pt, notes insidious memory impairment.
Pts have difficulties learning and retaining new information and handling complex tasks (e.g., balancing the checkbook), and they have impairments in reasoning, judgment, spatial ability, and orientation (e.g., difficulty driving, getting lost away from home).
Behavioral changes, such as mood changes and apathy, may accompany memory impairment. In later stages pts may develop agitation and psychosis.
Atypical presentations include early and severe behavioral changes, focal findings on examination, parkinsonism, hallucinations, falls, or onset of symptoms younger than the age of 65.
Pts with isolated memory loss who lack functional impairment at home or work do not meet criteria for dementia but may have mild cognitive impairment (MCI). Identifying pts with MCI is important because pts with MCI may have a slightly higher rate of progression to dementia.
The diagnostic evaluation should include the following:• An attempt at the Folstein Mini-Mental State Examination to screen for dementia and to document the progression of disease over time by repeating the test at 3- to 6-mo intervals (Table 10-14)
• One venipuncture for a profile of blood values: glucose, CBC, electrolytes, ALT, AST, BUN, Cr, VDRL, Ca, Mg, TSH, HIV (selected pts), B12 level, RBC folate
• Depending on PE and hx findings, other tests may include brain MRI, PET scan, and LP.
TABLE 10-14
The Mini-Mental State Examination (MMSE)
| Parameter | Score |
| Orientation: What is the month, day, date, year, season? Where are you? What floor, city, country, state? (Score 1 point for each item correct.) | 10 |
| Registration: State three items (ball, flag, tree). (Score 1 point for each item that the pt registers without your having to repeat the words. You may repeat the words until the pt is able to register the words, but do not give the pt credit. You must also tell the pt that he/she should memorize those words and that you will ask him/her to recall those words later.) | 3 |
| Attention: Can you spell the word WORLD forward, then backward? Can you subtract 7 from 100, and keep subtracting 7? (100-93-86-79-72) (Do both items but give credit for the best of the two performances.) | 5 |
| Memory: Can you remember those three words I asked you to memorize? (Do not give clues or multiple choice.) | 3 |
| Language: | |
| Naming: Can you name (show) a pen and a watch? | 2 |
| Repetition: Can you repeat “No ifs, ands, or buts”? | 1 |
| Comprehension: Can you take this piece of paper in your right hand, fold it in half, then put it on the floor? (Score 1 point for each item done correctly.) | 3 |
| Reading: Read and obey “Close your eyes.” | 1 |
| Writing: Can you write a sentence? | 1 |
| Visuospatial: Have pt copy intersecting pentagons. | 1 |
| Total | 30 |
Interpretation: Traditionally, with use of a cutoff score of 23 of 30, the sensitivity and specificity of the MMSE have been reported to be 87% and 82%, respectively, for detection of delirium or dementia in hospitalized pts. However, cognitive performance as measured by the MMSE varies within the population by age and education. To adjust for these variables, it has been proposed that a cutoff score of 19 is appropriate for pts with 0 to 4 years of education and will identify those individuals performing below the level of 75% of their peers; the cutoff score should be 23 for those with 5 to 8 years of education and 27 for those with 9 to 12 years of education. A score <29 would be abnl in 75% of individuals with a college education.
Modified from Folstein MR, Folstein SE, McHugh PR: “Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189, 1975.
Of great importance is the identification of treatable causes of dementia:• Drug induced
• Depression
• Hypothyroidism
• Hyperthyroidism
• Hypoglycemia
• Vitamin B12 or folate deficiency
• Subdural hematoma
• Liver failure
• NPH
• Stroke
• CNS infections
• Other infection
• Cerebral neoplasm
• Renal failure
• Ethanol abuse
• Hypoxia
• Hypercalcemia
• Vasculitis
• Cardiopulmonary disorders
• Severe anemia
Treatment
Pursue the causes.
Avoid restraints, but use them for safety if necessary.
Control hyperactivity of delirium w/haloperidol. Administer 0.5 to 1 mg IM, IV, or PO initially and the observe pt for 20 to 30 min. If the pt remains unmanageable but has not had any adverse reactions to haloperidol, double the dose and continue monitoring. Lorazepam 1 mg IM qh may also be administered if needed, but it often has a paradoxical effect in elderly pts.
Donepezil, rivastigmine, and galantamine are reversible acetylcholinesterase inhibitors approved for Rx of mild to moderate dementia of Alzheimer’s type. They may be helpful in delaying the progression of Alzheimer’s disease if used in the early stages. They can provide modest improvement of sx and temporary stabilization of cognition by lengthening the time from assisted community living to nursing home placement. Memantine is an N-methyl-D-aspartate (NMDA) receptor blocker indicated for the Rx of moderate to severe Alzheimer’s disease. It can produce slight improvements in cognitive performance. The clinical significance of these improvements is small. Memantine can be used in combination w/anticholinesterase inhibitors.G. Multiple Scerosis (MS)
Chronic autoimmune demyelinating disease of the CNS characterized by clinical attacks (relapses) correlated w/lesions separated in time and space. A relapse is the subacute onset of neurologic dysfunction that lasts for ≥24 hr. Subtypes of MS include the following: relapsing-remitting MS (RRMS), relapses followed by complete or nearly complete recovery; secondary progressive MS (SPMS), progression of disability w/few or no relapses; and primary progressive MS (PPMS), progression from onset. Rare MS variants include the following: Balo’s concentric sclerosis, alternating rings of myelination and demyelination; Marburg’s disease, tumor-like lesion w/significant edema; and Schilder’s diffuse sclerosis, childhood onset w/one to two large, symmetric lesions. Neuromyelitis optica (Devic’s disease) involves primarily the optic nerves and spinal cord and is considered a separate disease.
Table 10-16 summarizes the McDonald criteria for MS.
TABLE 10-16
Summary of Revised 2005-2010 McDonald Criteria for Diagnosis of MS
| Clinical Attacks | Clinical Lesions | Paraclinical Testing Needed |
| 2 | 2 | None |
| 2 | 1 | MRI dissemination in space or two lesions on MRI consistent with MS plus positive CSF |
| 1 | 2 | MRI dissemination in time |
| 1 | 1 | MRI dissemination in space or two MRI lesions consistent with MS and positive CSF and MRI dissemination in time |
| Evidence of clinical lesions by physical examination or evoked potentials. | ||
| Diagnosis of PPMS: 1 year evidence of disease progression and two of the following: | ||
| (1) evidence for dissemination in space, (2) evidence for dissemination in time, or (3) positive CSF | ||
| MRI dissemination in space, by either (1) one or more T2 lesion in two of the four typical areas for MS lesions (periventricular, juxtacortical, infratentorial, or spinal cord) or (2) awaiting further clinical attack implicating a distinctly separate CNS region. MRI dissemination in time, a new enhancing lesion ≥3 mo or a new nonenhancing lesion ≥6 mo after the initial attack; positive CSF, positive oligoclonal bands or elevated immunoglobulin G index. | ||
Modified from Degenhardt A: Ferri’s Clinical Advisor, 2013. St. Louis, Mosby, 2012, p. 700. Incorporates 2010 Revisions to Diagnostic criteria of MS (for details, please see original article: Polman CH, Reingold SC, Banwell B, et al: Diagnostic criteria for multiple sclerosis: 2010 revisions to McDonald’s criteria. Ann Neurol 69:292-302, 2011).
Diagnosis
MS: based on revised 2005 McDonald criteria (see Table 10-16)
RRMS: at least two relapses—two clinical lesions distinctly separated in space and time or one clinical lesion plus paraclinical testing
PPMS: insidious progression of disability with a positive CSF and either dissemination in both space and time or ongoing progression for ≥1 yrH&P
Visual abnlities• Paresis of medial rectus muscle on lateral conjugate gaze (internuclear ophthalmoplegia) and horizontal nystagmus of the adducting eye
• Central scotoma, ↓ visual acuity (optic neuritis)
• A Marcus Gunn pupil (pupil that paradoxically dilates w/direct light), indicating damage to the optic nerve anterior to the chiasm, is frequently present.
• Nystagmus
Abnlities of reflexes• ↑ DTRs
• (+) Hoffmann’s sign, (+) Babinski’s reflex
• ↓ Abd skin reflex, ↓ cremasteric reflex
Lhermitte’s sign: flexion of the neck while the pt is lying down elicits an electrical sensation extending bilaterally down the arms, back, and lower trunk.
Uhthoff’s phenomenon: exercise- or heat-induced deterioration of function
Charcot’s neurologic triad: nystagmus, scanning speech, and intention tremor
Impaired recognition of objects by touch alone (astereognosis)Imaging
MRI of brain w/gadolinium can identify lesions as small as 3 to 4 mm and is used to assess disease load, activity, and progression.
MRI reveals multiple, predominantly periventricular plaques; however, normal MRI cannot be used to exclude MS.
MRI of the cervical spine can also be helpful.Labs
LP for all first relapses when the dx of MS is not definite. Possible CSF abnlities include ↑ protein and mononuclear WBCs (both usually only mild). CSF IgG index and (+) oligoclonal bands are seen in 70% and 90%, respectively, of clinically definite MS cases. False(+) results occur w/IgG index in CNS infections and inflammation but rarely w/oligoclonal bands.
Serum: CBC, ESR, CRP, CHEM 7, LFTs, ANA, vitamin B12, Lyme titer, TSH
Treatment
Acute General Rx
Relapses: high-dose IV methylprednisolone (3-5 days of 1 g/day; alternative dose is 15 mg/kg/day), often followed by a 7- to 10-day prednisone taper. No evidence suggests that high-dose corticosteroids alter the long-term course of disease.
If pt has marked acute disability and acute corticosteroid therapy has failed, plasma exchange (5 to 7 exchanges on alternate days) have shown benefit.Chronic Treatment
Disease-modifying therapy: includes interferon-β1a, interferon-β1b, and glatiramer acetate. Interferons require routine CBC and LFT checks (initially in 1 mo, q3mo thereafter), occasionally TSH. None are needed with glatiramer acetate. Interferons can frequently cause flulike symptoms.
Fingolimod, a sphingosine-1-phosphate receptor modulator, is approved as the first oral disease-modifying agent. Common side effects are liver toxicity, bradycardia with the first dose only, and pancytopenia. Its use may be reasonable in pts who cannot tolerate or do not benefit from alternative disease-modifying therapies and in those who have had one or more relapses or new white-matter lesions on MRI within the past year.
Dalfampridine is a potassium channel blocker approved to improve walking speed in patients with MS.
Cytotoxic: Methotrexate or azathioprine is occasionally used in RRMS or PPMS. Consider cyclophosphamide or mitoxantrone (causes dose-dependent cardiotoxicity) for frequent relapses with significant disability progression and for early secondary progressive MS. Emerging potential agents with long-term immunosuppressive effects include cladribine, alemtuzumab, daclizumab, laquinimod, and teriflunomide.
Monoclonal antibodies: Natalizumab is approved for treatment of RRMS in the form of monthly infusions. It has been associated with an increased risk of developing progressive multifocal leukoencephalopathy (rare and fatal brain infection). Pts taking natalizumab must enter into a registry for monitoring.
Spasticity: Onabotulinum toxin type A injection is FDA approved as first-line therapy for upper limb spasticity. Baclofen, tizanidine, dantrolene diazepam, lorazepam, and intrathecal baclofen are other alternatives.
Pain: carbamazepine, gabapentin, or amitriptyline
Spastic bladder: oxybutynin, tolterodine, or propantheline; prazosin for spastic sphincter
Fatigue: Consider amantadine 100 mg bid, modafinil (most effective for somnolence), or fluoxetine.
Tremor: clonazepam, carbamazepine, propranolol, or gabapentin. Wrist splints may be helpful.H. Disorders of the Spinal Cord
1. Compressive Myopathies
Spinal cord compression is the neurologic loss of spine function. Lesions may be complete or incomplete and develop gradually or acutely. Incomplete lesions often are manifested as distinct syndromes, as follows:• Central cord syndrome
• Anterior cord syndrome
• Brown-Séquard syndrome
• Conus medullaris syndrome
• Cauda equina syndrome
Etiology
Trauma
Tumor
Infection
Inflammatory processes
Degenerative disk conditions w/spinal stenosis
Acute disk herniation
Cystic abnlitiesDiagnosis
H&P
Clinical features reflect the amount of spinal cord involvement:
Central cord syndrome: variable quadriparesis, w/UEs more severely involved than the LEs; some sensory sparing
Anterior cord syndrome: motor, pain, and temperature loss below the lesion
Brown-Séquard syndrome• Caused by injury to either half of the spinal cord and resulting in the loss of motor function, position, vibration, and light touch on the affected side
• Pain and temperature sense loss on the opposite side
Conus medullaris syndrome: variable motor loss in the LEs w/loss of bowel and bladder function
Cauda equina syndrome: typical low back pain, weakness in both LEs, saddle anesthesia, and loss of voluntary bladder and bowel controlImaging
MRITreatment
Urgent surgical decompression2. Infectious Myopathies
HIV infection
Viral myositis
Trichinosis
Toxoplasmosis
Cysticercosis
Bacterial infections3. Inflammatory Myopathies
SLE, RA
Sarcoidosis
Paraneoplastic syndrome
Polymyositis, dermatomyositis
Polyarteritis nodosa
MCTD
Scleroderma
Inclusion body myositis
Sjögren’s syndrome
Cimetidine, D-penicillamine4. Endocrine-Related Myopathies
Corticosteroid-Induced Myopathy
Proximal limb weakness (mostly legs) in chronic corticosteroid ptsDemographics
Women affected ×2 as men
↑ Risk use high-dose (≥30 mg/day) prednisoneDiagnosis
Cushingoid body habitus
Neurologic exam: intact ocular, facial, distal extremity strength; nl sensory exam and DTRs
Labs: serum CK and EMG results nl (↑ CK or abnl EMG suggests recurrence of partly Rx myositis or another myopathy)
Muscle biopsy: non-dx, only shows atrophy type IIb muscle fibersTreatment
Slow tapering of corticosteroid Rx with discontinuationThyrotoxic Myopathy
Symmetric muscle weakness in pts with classic hyperthyroidism or hypothyroidismClinical and Presentation and Treatment
Toxic Myopathies
Clinical presentation of proximal muscle weakness, myalgia, and cramps should prompt review of current medications (statins) as a recent ↑ dosage, switch, or addition can ↑ myopathy risk.
Concomitant use of drugs that inhibit CYP3A4 (macrolides, cyclosporine, itraconazole, protease inhibitors) will ↑ risk myopathies in pts taking lovastatin, simvastatin, atorvastatin. In these pts, pravastatin, rosuvastatin, or fluvastatin (differently metabolized) may be preferable.5. Idiopathic Transverse Myelitis
Demyelination in a transverse region of the spinal cord due to an inflammatory process leading to sensory and motor changes below the lesion
Etiology
Demyelination due to the body’s immune response to infection, post-vaccination, may be onset of multiple sclerosis (MS), or may be idiopathic (15%30% of cases).• About 50% of pts have had a recent URI.
• EBV and CMV are most common viral infections.
• Hepatitis B, varicella, enterovirus, rhinovirus, mycoplasma, syphilis, measles, Lyme disease are less common.
Diagnosis
Transverse myelitis should be suspected in pts with a hx of rapid (hr to days) onset of motor weakness, sensory abnlities referable to the spinal cord, and bladder or bowel dysfunction. The dysfunction is bilateral (not necessarily symmetric) and there is a clearly defined sensory level.
LP looking for oligoclonal bands for MS or infection
MRI of brain and MRI of spine at level of suspected involvementH&P
The clinical signs are caused by an interruption in ascending and descending neuroanatomic pathways in the transverse plane of the spinal cord and a resulting sensory level is characteristic of transverse myelitis.
Rapid onset of symmetric or asymmetric paraparesis or paraplegia of the lower extremities over a few days, ascending paresthesia, trunk sensory level, back pain, sphincter dysfunction, and (+) Babinski with upgoing toes bilaterally. The arms may also be involved but < the legs in most cases.
One third to one half of pts present with localizing back pain.
There is progression to nadir of clinical deficits between 4 hr and 21 days after symptom onset.Labs
CSF: ↑ protein/nl protein, lymphocytes, and nl glucose
Serum NMO-IgG to w/up neuromyelitis optica, which should be ruled out.
Oligoclonal bands should be absent in CSF in transverse myelitis and (+) in MS.
Liver enzymes may help to differentiate if it is postinfectious transverse myelitis versus MS.
Consider autoimmune w/up for lupus.Treatment
High-dose IV corticosteroid (e.g., methylprednisolone 1000 mg/day for 3-5 days)
Rescue Rx with plasma exchange may be helpful in pts who do not respond to corticosteroids.
Combination Rx with plasmapheresis and immunosuppressive agents (e.g., cyclophosphamide) may also be effective.
Naproxen, ibuprofen for painI. Peripheral Neuropathies
1. General Approach
Figure 10-4 describes a systematic approach to evaluate neuropathy.
2. Mononeuropathies
a. Carpal Tunnel Syndrome
Compressive neuropathy of the median nerve as it passes under the transverse carpal ligament at the wrist. It is the most common entrapment neuropathy.
Diagnosis
Pain, paresthesia in the first, second, and third fingers and the lateral half of the fourth finger, worse at night
FIGURE 10-4 A systematic approach to evaluate neuropathy. The diseases listed are examples of neuropathies associated with specific neurophysiologic and clinical findings. Diabetic distal, predominantly sensory neuropathies are manifested as chronic axonal neuropathies; acute asymmetric neuropathies can also occur with diabetes. Most neuropathies caused by toxins or by side effects of medication are chronic, symmetric axonal neuropathies. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN) are subtypes of Guillain-Barré syndrome. These and other examples are discussed in more detail in the text. CIDP, chronic inflammatory polyradiculoneuropathy; CIP, chronic illness polyneuropathy; CMT1, Charcot-Marie-Tooth disease type 1, a genetic disorder; ENMG, electroneuromyography; HIV, human immunodeficiency virus–related neuropathy; α−MAG, anti–myelin-associated glycoprotein; MMN, multifocal motor neuropathy. (From Goldman L, Schafer AI [eds]: Goldman’s Cecil Medicine, 24th ed. Philadelphia, Saunders, 2012.)
Tinel’s sign at wrist: Tapping lightly over the median nerve on the volar surface of the wrist produces a tingling sensation radiating from the wrist to the hand.
Phalen’s sign: reproduction of sx after 1 min of gentle, unforced wrist flexion
EMG: impaired sensory conduction across the carpal tunnelTreatment
Activity modification
Nocturnal wrist splint
Corticosteroid injection of carpal canal on ulnar side of palmaris longus tendon proximal to wrist crease
Short-term benefit from U/S Rx
Ergonomic keyboards (vs standard keyboards)
Surgery in refractory casesb. Bell’s Palsy
Acute peripheral facial (seventh) nerve palsy
Etiology
HSV is thought to be the most common viral pathogen, followed by herpes zoster.Diagnosis
Onset is usually acute to subacute over hours of unilateral facial paralysis with maximal weakness at 3 wk. One third of pts demonstrate incomplete paralysis, whereas the remaining two thirds have complete paralysis. Recovery is present within the first 6 mo.Treatment
Glucocorticoid Rx: prednisone 60 to 80 mg/day for 1 wk
Disposition
71% of pts: complete recovery
Recurrence rate is 7%. Average time to recurrence is 10 yr.3. Polyneuropathies
a. Diabetic Neuropathy
Diagnosis
EMG can be helpful in confirming the presence, extent, and severity of neuropathy.H&P
Distal symmetric polyneuropathy (DSPN)• Pts most commonly experience numbness and tingling but may also experience feelings of tightness or a sensation of heat or cold.
• Pain is not uncommon, is often worst at night, and can be burning, aching, shooting, or lancinating.
• These sx begin in the feet and may slowly ascend over months to years. Sx in the hands do not generally occur until sx in the lower extremities have reached the level of the knees. In more severe cases, the sx can spread to the trunk and head.
• Neurologic examination reveals early loss of small-fiber modalities resulting in ↓ pinprick and temperature sensation with later involvement of large-fiber modalities leading to a reduction in vibratory and proprioceptive sensation. Ankle reflexes are usually ↓ or absent, and more proximal reflexes may also become involved as the neuropathy progresses. Strength is usually nl, but there can be some motor involvement leading to mild weakness and atrophy, which are usually limited to intrinsic foot muscles and ankle dorsiflexors.
Autonomic neuropathy• GI sx are common and can include early satiety, bloating, vomiting, constipation, or diarrhea.
• Cardiovascular complications include cardiac arrhythmias and postural hypotension.
• Pts may also have sx related to dysfunction of the GU (erectile dysfunction and incontinence) or thermoregulatory (excessive or ↓ sweating, intolerance of cold or heat) systems.
Regional diabetic polyneuropathy• The most common presentation is diabetic lumbosacral radiculoplexus neuropathy, which is also known as diabetic amyotrophy or Bruns-Garland syndrome. Pts usually report acute or subacute onset of severe pain involving the lower back, hip, and thigh.
• Weakness and atrophy of the affected leg progress over the course of days to weeks, often predominantly in the anterior thigh.
Focal diabetic neuropathy• Diabetic pts are at ↑ risk for common limb mononeuropathies, particularly median neuropathy at the wrist and ulnar neuropathy at the elbow, but other nerves (femoral, sciatic, or peroneal) may be involved as well.
Treatment
Topical agents: Lidocaine 5% patch can be applied to painful areas for 12 hr a day.
Anticonvulsants: gabapentin (100-1200 mg tid) and pregabalin (50-100 mg tid)
Antidepressants: amitriptyline (10-100 mg qhs), nortriptyline (25-150 mg qhs), and duloxetine (60-120 mg daily)b. Charcot-Marie-Tooth Disease (CMT)
Heterogeneous group of noninflammatory inherited peripheral neuropathies characterized by chronic motor and sensory polyneuropathy. It is the most common inherited neuromuscular disorder. Transmission may be autosomal dominant, autosomal recessive, or X-linked, with some sporadic cases reported.
Diagnosis
Symmetric, slowly progressive distal motor neuropathy resulting in weakness and atrophy in legs, often progresses to involve hands
High-arched feet (pes cavus), claw toe deformities, and hammer toes
Atrophy of the lower legs producing a storklike appearance (muscle wasting does not involve the upper legs)
↓ Proprioception and weakness of ankle dorsiflexors often interfere with balance and gait (steppage gait)Treatment
Symptomatic and supportive care is managed by a multidisciplinary team including physical and occupational Rx.
Musculoskeletal pain may respond to acetaminophen or NSAIDs; neuropathic pain may respond to tricyclic antidepressants or drugs such as carbamazepine or gabapentin.
Occasionally, orthopedic surgery is required to correct severe pes cavus deformity or hip dysplasia.c. Guillain-Barré Syndrome (GBS)
Acute inflammatory demyelinating polyradiculopathy predominantly affecting motor function. GBS is the most common cause of acute ascending flaccid paralysis.
Etiology
Most pts give h/o respiratory (mycoplasma)/GI illness (Campylobacter jejuni) within 30 days of neurologic sx onset.Diagnosis
History
Rapid progression of acute symmetric progressive weakness, usually > distally than proximally and > in the legs than in the arms
The pt often reports difficulty in ambulating, getting up from a chair, or climbing stairs.
The ascending paralysis affects motor nerves more than sensory nerves. Sensory loss (predominantly position and vibration senses) is variable but usually mild.
In some pts, the initial manifestations may involve the cranial musculature or the UEs (e.g., tingling of the hands).
As a general rule, weakness reaches its max within 14 days.Physical Exam
Symmetric weakness, initially involving proximal muscles, subsequently both proximal and distal muscles
↓ Or absent reflexes bilaterally early in the disease
Minimum to moderate glove and stocking anesthesia
Ataxia and pain in a segmental distribution possible in some pts (caused by involvement of posterior nerve roots)
Autonomic abnlities (bradycardia or tachycardia, hypotension or HTN) also possible
Respiratory insufficiency (caused by weakness of intercostal muscles)
Facial paresis, difficulty swallowing (secondary to cranial nerve involvement)Labs
LP: Typical findings include ↑ CSF protein (especially IgG) and presence of few mononuclear leukocytes (albuminocytologic dissociation).EMG/NCS
Slowed conduction velocities; motor, sensory, and F wave latencies. EMG may be nl in first 7 to 10 days.Treatment
Close monitoring of respiratory function (frequent [q1h initially] bedside measurements of FVC and (−) inspiratory force to assess pulmonary muscle strength) because respiratory failure is the major potential problem in GBS.
Infusion of IVIG (0.4 g/kg/day for 5 days). Always check serum IgA levels before infusion to prevent anaphylaxis in deficient pts.
Plasma exchange: 200 to 250 mL/kg during five sessions qod
IVIG and plasma exchange are equally effective. The selection of one or the other is determined by availability and risk of particular complications. For example, plasma exchange should be avoided in pts w/prominent autonomic dysfunction.
There is no proven benefit of combining IVIG and plasma exchange.
Ventilatory support may be necessary in 10% to 20% of pts. Adequate fluid/electrolyte support and nutrition are necessary, especially in pts w/dysautonomia or bulbar dysfunction.
Aggressive nursing care is required to prevent decubitus ulcers, infections, fecal impactions, and pressure nerve palsies and for mouth care to prevent ventilator-associated pneumonias.
Monitor and treat autonomic dysfunction (bradyarrhythmias or tachyarrhythmias, orthostatic hypotension, systemic HTN, altered sweating).
Treat back pain and dysesthesia w/low-dose tricyclic antidepressants, gabapentin, and the like. Opiate narcotics can be used cautiously in the short term but may compound dysautonomia.
DVT prophylaxisd. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Symmetric proximal and distal weakness with associated sensory loss along with ↓ or absent reflexes for >2 mo
Diagnosis
NCS: features of demyelination including prolonged distal latencies and F-waves, slowed velocities, and at least one nerve demonstrating partial conduction block (feature of acquired demyelination)H&P
Characterized by occurrence of symmetric weakness in both proximal and distal muscles that progressively ↑ over 2 mo
Associated with impaired sensation, postural instability, ↓ or absent DTRs, and variable craniofacial-bulbar involvementLabs
CSF analysis to assess for albumin-cytologic dissociation (i.e., ↑ protein with nl cell count), along with appropriate laboratory studies to exclude associated conditionsTreatment
IVIG, plasmapheresis/plasma exchange, and corticosteroids. There is no difference in efficacy among these three modalities of Rx.
Azathioprine, mycophenolate mofetil, cyclophosphamide, rituximab, and cyclosporine may be used as secondary agents.J. Amyotrophic Lateral Sclerosis (ALS)
Progressive, degenerative neuromuscular condition of undetermined etiology affecting corticospinal tracts and anterior horn cells and resulting in dysfunction of both UMN and LMN, respectively
Etiology
90% to 95% sporadic
Of the familial cases, 10% to 20% associated w/genetic defect in copper-zinc superoxide dismutase enzymeDiagnosis
EMG and NCS (El Escorial criteria)
Assessment of respiratory function (forced vital capacity [FVC], [−] inspiratory force)H&P
LMN signs: weakness, hypotonia, wasting, fasciculations, hyporeflexia or areflexia
UMN signs: loss of fine motor dexterity, spasticity, extensor plantar responses, hyperreflexia, clonus
Preservation of extraocular movements, sensation, bowel and bladder function
Dysarthria, dysphagia, pseudobulbar affect, frontal lobe dysfunction
Respiratory insufficiency, typically late in the disease
ALS comprises approximately 90% of adult-onset motor neuron diseases. Other presentations of motor neuron disease include progressive muscular atrophy, primary lateral sclerosis, progressive bulbar palsy, progressive pseudobulbar palsy, and ALS-parkinsonism-dementia complex.Labs
Vitamin B12, thyroid function, parathyroid hormone, HIV may be considered.
Serum protein and immunofixation electrophoresis
DNA studies for SMA or bulbospinal atrophy, hexosaminidase levels in pure LMN syndrome
24-hour urine for heavy metals if indicatedImaging
MRI to r/o brain and spinal cord disorders
Modified barium swallow to evaluate aspiration riskTreatment
PEG tube placement improves nutritional intake, promotes weight stabilization, and eases medication administration.
Nutrition, speech Rx, physical and occupational Rx services are indicated.
Suction device is used for sialorrhea.
Communication may be eased with computerized assistive devices.
Early discussion should cover living will, resuscitation orders, desire for PEG and tracheostomy, potential long-term care options.
Riluzole, a glutamate antagonist, is the only FDA-approved medication known to extend tracheostomy-free survival in pts with ALS.
Spasticity may be treated pharmacologically with baclofen, tizanidine, clonazepam.
Pseudobulbar affect may improve with amitriptyline, sertraline, or dextromethorphan/quinine.Disposition
Mean duration of sx is 3 to 5 yr.
Approximately 20% of pts survive >5 yr.K. Neuromuscular Junction Disorders
1. Myasthenia Gravis (MG)
Acquired autoimmune disorder of neuromuscular transmission characterized by the presence of a γ-globulin Ab (AChR-Ab) directed against postsynaptic acetylcholine receptor or against muscle-specific tyrosine kinase (MuSK) receptors
Diagnosis
H&P
The hallmark of MG is weakness made worse w/exercise and improved by rest. Sx fluctuate and are often better in the morning.
>50% of pts present initially w/ptosis, ocular muscle weakness, or both.
Pts have difficulty in chewing, abnl smile, dysarthria, dysphagia.
Involvement of the respiratory muscles may require intubation and assisted ventilation.
Pain may occur in fatigued muscles (e.g., neck muscles).
Clinical manifestations reproducible w/exercise. Observation of the pt performing repetitive muscle contractions of involved muscles will demonstrate rapidly developing weakness.
PE may be nl at rest.
Pts w/h/o ptosis will demonstrate fatigue weakness and ptosis when asked to sustain upward gaze for >3 min w/o interruption.Labs and Other Tests
Edrophonium test: improvement of sx after use of anticholinesterase medications (edrophonium)
EMG: single-fiber electromyography: sensitivity >90 % but nonspecific
MRI or CT of anterior mediastinum: thymoma found in 12%
TSH: thyroid disease found in 30% of pts
Vitamin B12 level: r/o pernicious anemia
ANA, RF ( association w/SLE, RA)
(+ ) Ab against MuSK receptorsTreatment
Acetylcholinesterase inhibitors: Pyridostigmine is first-line Rx.
Immunosuppressants: corticosteroids, azathioprine, mycophenolate mofetil, rituximab for more severe or generalized disease
Plasmapheresis and IVIG in refractory cases
Thymectomy in thymomatous MG2. Lambert-Eaton Myasthenic Syndrome
Disorder of neuromuscular transmission caused by Ab against presynaptic voltage-gated P/Q Ca channels on motor and autonomic nerve terminals. The two forms are paraneoplastic (most common, small cell lung cancer 50-70%) and nonparaneoplastic (autoimmune).
Diagnosis
H&P
Weakness w/↓ or absent muscle stretch reflexes
Proximal LE muscles affected most
Transient strength improvement w/brief exercise
Autonomic dysfunction common (dry mouth in 75%, sexual dysfunction, blurred vision, constipation, orthostasis)
Treatment
Acute: plasma exchange (200-250 mL/kg over 10-14 days) or IVIG (2 g/kg over 2-5 days)
Chronic Rx: anticholinesterase agents (pyridostigmine )L. Head Injury
1. Epidural Hematoma
Collection of blood between the skull and dura mater (Fig. 10-5)
FIGURE 10-5 Epidural hematoma. The arrows show the pattern of brain displacement. (From Weissleder R, Wittenberg J, Harisinghani M, Chen JW [eds]: Primer of Diagnostic Imaging, 5th ed. St. Louis, Mosby, 2011.)
Etiology
Head trauma causing temporal bone fracture resulting in middle meningeal artery tear
Neoplasms that have spread into the epidural spaceDiagnosis
H&P
Lucid interval after the head trauma is followed by progressive reduction in the level of consciousness as the hematoma enlarges and the underlying brain is displaced inward.
The initial injury causes brain concussion and loss of consciousness from which the pt awakens and may have some headache but seems otherwise to have recovered.
Downward transtentorial herniation may develop rapidly, causing third nerve compression and an ipsilateral hemiparesis.Imaging
Brain CTTreatment
Emergency surgical evacuation2. Subdural Hematoma
Bleeding into the subdural space, caused by rupture of bridging veins between the brain and venous sinuses (especially where stretched by underlying cerebral atrophy). Figure 10-6 illustrates subdural hematoma and compares it with epidural hematoma.
Diagnosis
H&P
Vague headache, often worse in morning than evening
Some apathy, confusion, and clouding of consciousness is common, although frank coma may complicate late cases. Chronic subdural hematomas may cause a dementia picture.
Neurologic sx may be transient, simulating TIA.
Almost any sign of cortical dysfunction may occur, including hemiparesis, sensory deficits, and language abnlities, depending on which part of the cortex is compressed by the hematoma.
FIGURE 10-6 Subdural hematoma and comparison with epidural hematoma. (From Weissleder R, Wittenberg J, Harisinghani M, Chen JW [eds]: Primer of Diagnostic Imaging, 5th ed. St. Louis, Mosby, 2011.)
Labs
Hct, Plt count, PTT, and PT/INRImaging
CT of brainTreatment
Small subdural hematomas may be left untreated and the pt observed; but if there is an underlying cause, such as anticoagulation, this should be rapidly corrected to prevent further accumulation of blood.
Neurosurgical drainage of blood from subdural space through burr hole is the definitive procedure, although it is common for the hematoma to reaccumulate.3. Concussion
Complex pathophysiologic process affecting the brain. When traumatic biomechanical rotational/angular acceleration forces are applied to the brain, they cause shear strain of underlying neural elements. Although not required, it may be associated with direct trauma.
Concussions typically result in rapid onset of a short-lived neurologic functional deficit that spontaneously resolves. Chronic injury may result in long-term neuropathologic changes.
Concussion results in a graded set of clinical syndromes that may or may not involve loss of consciousness. Table 10-17 describes commonly used grading scales for concussion. Resolution of the clinical sx typically follows a sequential course. It is typically associated with grossly nl structural neuroimaging.Diagnosis
Workup
Sideline assessment• Neurologic assessment uses a standardized tool, such as SCAT2 (Sport Concussion Assessment Tool) or SAC (Standardized Assessment of Concussion).
• Monitor for deterioration; no athlete should be left alone.
Neurocognitive testing• Computer-based programs, such as ImPACT, ANAM, CogSport
• Neuropsychiatric testing administered by a neuropsychologist
Gait/balance testing with a tool such as the Balance Error Scoring System (BESS)TABLE 10-17
Grading Scales for Concussion
| Scale | Grade of Concussion | ||
| I | II | III | |
| Colorado | Confusion; no LOC; PTA <30 min | LOC <5 min; confusion; PTA >30 min | LOC >5 min; PTA >24 h |
| Cantu | PTA <30 min; no LOC | LOC <5 min; PTA 30 min to 24 h | LOC >5 min; PTA >24 h |
| AAN | Transient confusion; symptoms <15 min; no LOC | No LOC; transient confusion; symptoms >15 min | Any LOC |
AAN, American Academy of Neurology; LOC, loss of consciousness; PTA, posttraumatic amnesia.
Modified from Vincent JL, Abraham E, Moore FA, et al (eds): Textbook of Critical Care, 6th ed. Philadelphia, Saunders, 2011.
When used in combination, symptom assessment, balance assessment, and neurocognitive testing provide a sensitivity of >90% for the identification of concussion.Imaging
Head CT or MRI for grade II or III concussion with persistent abnlities on exam or symptoms lasting >1 wkTreatment
Immediate removal of athlete from game/athletic activity
Physical rest: no return to play until asymptomatic for atleast 24 hours
Cognitive rest to limit sx• Modifications at school
• Modifications at home/recreation
• Sleep encouraged
