and E. Lee Murray, MD
CHAPTER CONTENTS
SPASTICITY
Spasticity is common with a wide range of neurologic diseases. Management can be difficult and is almost always multimodal, although not all patients need treatment other than maintaining activity. However, management is considered especially when the patient has intractable pain or significant limitation of motion because of the spasticity.
Physical therapy should be considered first-line for almost all patients. The type and extent of therapy depend on the severity of the deficit.
Baclofen is a gamma aminobutyric acid (GABA) agonist commonly used for spasticity. Initial treatment is usually orally, but it is very effective intrathecally, given by continuous pump. Overdose can produce severe encephalopathy. A common starting dose is 5 mg t.i.d.
Benzodiazepines are commonly used, especially diazepam and clonazepam. They often cause sedation; this is most prominent initially and on dose increments.
Dantrolene is an alternative especially to baclofen. Because of the mainly peripheral action, it is less likely to produce cognitive effects at therapeutic doses. Starting dose is usually 25 mg/day.
Tizanidine is a newer agent that may produce less reduction in muscle function than the other agents described. Starting dose is often 2 mg q6-8h prn, max 3 doses/day.
Botulinum toxin injections is used for spasticity and focal spasms. Because of the size of the muscle mass involved, patients with widespread spasticity may not be a candidate for this treatment.
Surgery of various sorts can be done for spasticity. Some of these approaches can include contracture release, osteotomy, and implantation of a pump. Selective dorsal rhizotomy is considered for medically refractory cases.
INCREASED INTRACRANIAL PRESSURE
Intracranial pressure (ICP) can be increased from a wide variety of conditions discussed in this book. Generally, the causes fall into the following categories:
•Obstruction of CSF absorption
PRESENTATION depends on etiology and acuteness. Common symptoms include headache, nausea, vomiting, visual change including blurring or diplopia, and, ultimately, confusion, lethargy, and pupillary dilation. Diplopia from increased ICP is usually horizontal and due to abducens palsy. Visual change can be blurring to blindness. Papilledema is seen on exam unless the ICP increase is very acute. Additional brainstem findings can be from displacement and compression of neural structures as well as ICP itself.
DIAGNOSIS is discussed in depth throughout this book. Imaging is performed urgently when increased ICP is suspected.
MANAGEMENT is individualized on the basis of cause, acuity, and severity, but some general tools include:1
Cerebral edema from tumor or infection can be responsive to any of these. Edema from stroke or hypoxia does not respond well to corticosteroids.
Mass lesion without edema, such as large subdural hematoma, responds best to surgical evacuation, and, until this is performed, osmotic agents and hyperventilation can be helpful. Corticosteroids are less likely to be helpful.
Mass lesion with edema, such as from a large tumor with surrounding edema, may respond to corticosteroids, but this is not a replacement for treatment of the mass.
Focal edema from large stroke may have to be treated with craniectomy.
Sedation
Many patients with increased ICP have prominent encephalopathy or are in coma, but others may continue to have motor activity and appear restless.
The most commonly used agents include midazolam and lorazepam. Propofol is also used. Use of these may be limited by hypotension.
Corticosteroids
Corticosteroids are one of the cornerstones of management of increased ICP for many but not all conditions. They are effective for cerebral edema due to infection and tumor, but generally not for edema from stroke, hypoxia, or trauma.
Corticosteroids do not have an immediate effect. In times of critical increase in ICP, mannitol, hyperventilation, and/or surgery should be considered.
Decadron is used often starting at 10 mg IV × 1, followed by 4 mg IV q6h. Higher doses are often used.
Osmotic Agents
Mannitol is the most commonly used agent. This reduces the volume of brain tissue outside the lesioned area. Response occurs within minutes.
A common regimen is a 0.25–1.0 g/kg bolus with the higher dose used when critical ICP needs to be reduced as soon as possible. Maintenance dose is usually 0.25–0.50 g/kg q6h.
Serum osmolarity is measured and maintained typically in the range of 300–320 mOsm. Blood pressure is monitored because of the possibility of hypotension reducing cerebral perfusion pressure. Electrolytes are monitored closely.
When mannitol is no longer needed, it must be tapered to reduce the effects of rebound cerebral edema, since mannitol does open the blood–brain barrier.
Hypertonic saline is sometimes used, but mannitol is the preferred agent for most patients. Hypertonic saline may be preferential especially for patients with hypotension on admission.
Barbiturate Coma
Barbiturates are used less often than the other treatments discussed, but they still may be valuable for select patients. This is usually considered rescue therapy for refractory increased ICP. EEG monitoring is recommended, and the dose is adjusted to burst-suppression.
Hyperventilation
Hyperventilation (HV) reduces cerebral blood volume by vasoconstriction. However, the reduction is temporary. Also, the vasoconstriction may reduce perfusion pressure to areas of the brain. However, HV is still effective for producing an urgent reduction in ICP. HV should be avoided in stroke and head injury if possible.
Surgical Therapy
Ventricular drain is often performed especially when the cause of the increased ICP is at least partly hydrocephalus.
Craniectomy is performed especially when life-threatening cerebral edema needs to be decompressed to maintain perfusion pressure. This is usually unilateral (e.g., over an area of ischemia with edema). Bilateral craniectomy has rarely been performed as an acute life-saving attempt.
IMMUNE THERAPY
Immunosuppression has been discussed in multiple sections of this book. Here, we consider some general principles of immunosuppression. This is a rapidly moving field so current literature should be reviewed. Many uses are not FDA approved.
Neurologic conditions that may require immunosuppression in the hospital setting can include:
•Myasthenia gravis (MG): Especially myasthenic crisis but also for initial presentation
•Multiple sclerosis (MS): Usually as an acute attack in a patient with or without a known diagnosis of MS
•Acute inflammatory demyelinating polyneuropathy (AIDP): With initial presentation
•Chronic inflammatory demyelinating polyneuropathy (CIDP): With initial presentation or more commonly with exacerbation of known disease
•CNS vasculitis: Can be an initial diagnosis in a patient with stroke or with an exacerbation in a patient with known CNS vasculitis
•Temporal arteritis (TA): Usually with first diagnosis
•Optic neuritis (ON): For acute visual loss at initial presentation; less likely in a patient with prior demyelination
Neurologic complications of immunosuppression that may trigger neurologic evaluation in the hospital may be:
•Cancer induced by immunosuppressant, with neurologic involvement
Corticosteroids
Corticosteroids reduce the formation of a host of vasoactive substances.
MG is often treated with prednisone. Dose is gradually escalated because of the potential for worsening weakness early in administration. Ultimately, other agents such as azathioprine reduce the need for as much corticosteroids. Corticosteroids principally benefit systemic symptoms and less so ocular manifestations.
MS is often treated with high-dose corticosteroids for acute attacks. A common regimen is 1,000 mg methylprednisolone IV daily for 3–5 days, followed by a brief oral steroid taper. Oral methylprednisolone may be similarly effective for select patients.2
CIDP can be treated with corticosteroids, especially prednisone. This is used for chronic therapy rather than pulsed for acute therapy.
AIDP is not treated with corticosteroids. If there is concern that a patient presenting with a demyelinating neuropathy might have AIDP or CIDP, then corticosteroids should likely not be first-line: IV immunoglobulin (IVIg) or plasma exchange (PLEX) should be considered.
Temporal arteritis is treated initially with corticosteroids. A typical regimen starts with 40–60 mg/day prednisone PO. IV solumedrol is sometimes used.
Neuromyelitis optica (NMO) is a demyelinating disease that can be treated with high-dose corticosteroids initially. A common regimen is methylprednisolone as for MS attack.
Acute disseminated encephalomyelitis (ADEM) is an inflammatory disorder that is usually treated with high-dose corticosteroids. A common protocol is 1 g/day methylprednisolone IV for 3–5 days followed by an oral taper.
Interferons
Interferons are immune modulators that are used predominantly in neurology for MS. There are a multiplicity of biological actions that can contribute to the immunomodulatory effect.
MS is often treated with interferons as first-line disease-modifying therapy. These are usually not started in the hospital, although arrangements for insurance approval are often begun during the hospitalization.
Intravenous Immunoglobulin
IVIg is used for a host of neurologic diseases, especially for acute worsening of symptoms.
MG is often treated with IVIg for myasthenic crisis or for perioperative treatment.
AIDP can be treated with IVIg and is the first-line selection for many neurologists. Patients with more severe disease are often offered PLEX, although there is no data to indicate that one treatment is superior to the other. Treatment with both does not offer additional advantage.
CIDP can be treated with IVIg as part of initial therapy and for maintenance as pulsed treatment. Transient worsening of weakness can also be treated by IVIg.
MS attacks can be treated with IVIg if the patient cannot take corticosteroids. Supporting data are limited.
Azathioprine
Azathioprine is a purine antagonist antimetabolite used in neurology mainly for MG.
MG is often treated chronically with azathioprine after beginning corticosteroids. Ultimately, as the azathioprine shows sustained benefit, the effective dose of corticosteroids can be reduced.
NMO is often treated with corticosteroids initially, with the simultaneous institution of azathioprine.
Cyclophosphamide
Cyclophosphamide is an alkylating agent that is mainly used for neoplasms but also for select autoimmune diseases.
Primary CNS angiitis is treated with corticosteroids acutely with cyclophosphamide.
Methotrexate
Methotrexate is an antimetabolite that is used for cancers and select autoimmune diseases.
Primary CNS angiitis is usually treated with corticosteroids and cyclophosphamide, but methotrexate is also used.
NMO is sometimes treated by methotrexate, but azathioprine is used more commonly.
Plasma Exchange
PLEX is used for a wide variety of autoimmune diseases, and multiple neurologic conditions respond to plasma exchange:
MG can be treated with plasma exchange especially for myasthenic crisis. PLEX is often used for initial treatment as corticosteroid therapy is begun.
NMO has been treated with PLEX. This is supplemented by meds with a longer immunomodulatory effect such as azathioprine, methotrexate, or rituximab.
AIDP is commonly treated with PLEX. While this might be about equivalent to IVIg in effectiveness, many of us tend to use PLEX for patients more severely and rapidly affected. Combined treatment does not offer additional advantage.
MS can be treated with PLEX especially if symptoms are refractory to or patients cannot take the corticosteroids. Supporting data are limited.
Rituximab
Rituximab is a monoclonal antibody that binds to and destroys B-cells.
MG is not routinely treated with rituximab, but this has been used when patients have failed first- and second-line therapy, especially with anti-MuSK MG.
MS is usually treated with interferons or glatiramer. Rituximab may be effective for some patients and may be considered for patients with refractory disease. This is predominantly for patients with relapsing-remitting disease, although some patients with primary progressive MS may have a reduction in disease activity.
Other Immunosuppressants
There are many other immunosuppressents, and details of these are beyond the scope of this book. Also, this is a constantly changing field. Two agents are of potential importance to hospital neurology practice.
Fingolimod is the first oral med approved for relapsing-remitting MS. A principal risk is cardiac, with bradyarrhythmia and AV block. Because of this risk, the first dose must be administered with cardiac monitoring, potentially involving the hospital neurologist.
Natalizumab is a monoclonal antibody used for MS. This is not a first line treatment; it is usually used for patients with refractory disease. Risk of progressive multifocal leukoencephalopathy (PML) is of concern. When natalizumab is discontinued because of concern for PML, immune reconstitution inflammatory syndrome (IRIS) may develop.
