Brain and Cranial Nerve Disorders

Foundations

MS is an inflammatory disease of the central nervous system (CNS) manifested by demyelination of discrete regions (plaques) with a relative sparing of axons. An environmental trigger superimposed on genetic susceptibility appears to be a likely etiology. One theory proposes that this trigger establishes autoreactive T cells in the CNS that after a long latency period become reactivated on subsequent exposure to a systemic trigger, such as a viral infection or superantigen. This sets off a complex immunologic cascade that leads to demyelination.

MS presents with highly variable symptoms, making the illness difficult to definitively diagnose on a patient’s first presentation. Symptoms evolve over time with a broad range of severity. Women are more commonly affected than men, with a peak age of onset between 25 and 30 years. Management of MS continues to evolve, and early treatment with disease-modifying therapy results in improved outcomes. The emergency clinician will encounter patients with established diagnoses presenting with acute exacerbations (relapse) and undiagnosed patients presenting with initial symptoms. While familiarity with treatment options for managing relapse is necessary, arguably the most important role for the clinician is to recognize symptoms of MS and expedite testing and referral.

Clinical Features

The clinical picture in MS is one of marked heterogeneity. The classic clinical syndrome consists of recurring episodes of neurologic symptoms that rapidly evolve over days and slowly resolve over weeks. Variability occurs in age at onset, location of CNS lesions, frequency and severity of relapses, and degree and time course of progression. Four basic disease courses have been identified by the International Advisory Committee on Clinical Trials of MS. (2) The most common form is relapsing and remitting MS (RRMS, 85%), characterized by clearly defined attacks of new or increasing neurologic symptoms that are followed by periods of partial or complete recovery. The less common primary and secondary progressive MS syndromes are characterized by worsening neurologic function and accumulation of disability, either from symptom onset (primary), or after RRMS (secondary). The remaining course, radiologically isolated syndrome (RIS), has been used to classify those with radiographic abnormalities of MS who have no neurological symptoms or findings.

The clinical features of MS are divided into areas of specific CNS impairment and are described in Table 91.1 : cranial nerves, motor pathways, sensory pathways, cerebellar pathways, bowel/bladder/sexual dysfunction, and cognition. While MS has no single pathognomonic finding, optic neuritis has a particularly strong association with the disease. Optic neuritis is a unilateral syndrome characterized by pain in the eye and a variable degree of visual loss primarily affecting the central vision. It is the most common cranial nerve dysfunction related to MS, and not infrequently the first presenting symptom for which patients will seek care. It is the initial presentation in about 20% of MS patients. One study found that 65% of patients who presented to an ED with a first episode of optic neuritis were diagnosed with MS within one year. Other common cranial nerve symptoms include diplopia and nystagmus. The nystagmus may be severe enough to cause oscillopsia (a subjective oscillation of objects in the visual field). Cranial nerve impairment may also include impairment of facial sensation, which is relatively common. Unilateral facial paresis also may occur. In addition, the occurrence of trigeminal neuralgia in a young person may be an early sign of MS.

Motor pathways, specifically the corticospinal tract, are commonly involved. Paraparesis or paraplegia occurs with greater frequency than upper extremity lesions owing to the common occurrence of lesions in the motor tracts of the spinal cord. In patients with motor weakness, spasms of the legs and trunk may occur on attempts to stand from a seated position. This dysfunction is manifested on physical examination as spasticity that is typically worse in the legs than in the arms. The deep tendon reflexes are markedly exaggerated, and sustained clonus may be demonstrated. Although these symptoms may be bilateral, they are generally asymmetric. Sensory manifestations are a frequent initial feature of MS and will be present in nearly all patients at some point during the course of the disease. Sensory symptoms are commonly described as numbness, tingling, “pins and needles” paresthesias, coldness, or a sensation of swelling of the limbs or trunk.

Impairment of the cerebellar pathway may result in gait imbalance, difficulty with coordinated actions, and dysarthria. Physical examination reveals the typical features of cerebellar dysfunction, including dysmetria, dysdiadochokinesis (an impairment of rapid alternating movements), breakdown in the ability to perform complex movements, intention tremor in the limbs and head, truncal ataxia, and dysarthria. Impairment of bowel, bladder, and sexual function is also common with patients complaining of constipation, incontinence, and erectile dysfunction. Finally, cognitive impairments in MS are common, and may be underreported by patients, and underrecognized by care providers.

Differential Diagnoses

Given the marked heterogenicity of MS symptoms, the differential diagnosis is vast and includes central and peripheral nervous system disorders, ophthalmologic and neuropsychiatric disorders, and a large number of systemic and inflammatory/autoimmune disorders. Considerations will vary based on presenting symptoms, but may include ischemic and hemorrhagic stroke, CNS infection or malignancy, neuropathy, and rheumatologic conditions such as systemic lupus erythematosus. Several conditions can also present with radiographic features similar to MS. These include CNS tumors, spinal cord compression, vasculitides, Behçet disease, neuro-sarcoidosis, encephalomyelitis, HIV encephalopathy, Lyme disease, and vitamin B ₁₂ deficiency. The evolution of symptoms over time can be an important diagnostic finding in differentiating symptoms of MS from other conditions.

Diagnostic Testing

Patients previously diagnosed with MS presenting with acute exacerbations should be evaluated for an acute precipitating trigger, though most often one will not be found. The two most high-yield tests for diagnosing MS are a lumbar puncture (LP) and MRI of the brain and spinal cord. CT of the brain, with or without contrast, is not a useful test in evaluating MS but may be used to investigate other potential diagnoses. CSF analysis is abnormal in most cases of MS, but there is no definitive diagnostic biomarker and many of the more specialized CSF tests may not be done within the ED visit. Nevertheless, LP with CSF analysis can be useful in considering other causes of symptoms, and individual CSF proteins have been demonstrated to be biomarkers of disease activity and progression.

The initial imaging test to aid in the diagnosis of MS is gadolinium-enhanced MRI of the brain and spinal cord. MRI is a sensitive test for the detection of lesions consistent with MS and also is useful to assess disease severity. Lesions usually are multiple and commonly are found in the periventricular white matter. Recent studies point to the important role of ED MRI in patients with suspected MS: In one study, concordance between signs of demyelination of ED-based MRI and later final diagnosis of demyelinating disorder was approximately 52%. Given the importance of timely diagnosis and initiation of treatment, emergency clinicians should consider obtaining an MRI when feasible.

Management

Early treatment with disease-modifying therapies can lower relapse rates, reduce disability progression and improve survival. Management of MS in the ED typically entails treating MS relapse. Ongoing therapies, including disease-modifying therapies and management of MS-related complications are best made by a patient’s neurologist or primary care physician.

Treatment with high-dose IV corticosteroids diminishes the duration of symptoms and is an accepted best practice to manage MS relapse; however, there is no agreed upon best dosing regimens or durations of therapy. A common treatment regimen is IV methylprednisolone, 500 to 1000 mg daily for 3 to 5 days with or without a tapering dose of oral steroids (whether there is any benefit to divided doses versus a single daily dose is unclear).

There is an emerging body of evidence supporting the use of high-dose oral prednisone alone (typically 500 to 1250 mg daily) in the treatment of MS relapse. A recent meta-analysis failed to demonstrate clear-cut differences in efficacy and safety outcomes between oral and IV strategies. Outpatient oral prednisolone therapy may reduce health system and patient-borne expenses related to IV infusions, hospital stay, and lost work productivity, as well as minimize patient discomfort and improve patient satisfaction. The decision of oral versus IV therapy should ideally be made through shared decision-making and in consultation with the patient’s MS specialist. Other potential therapies of acute exacerbation include repository corticotrophin injection, plasmapheresis, and intravenous immunoglobulin.

Disposition

Patients with a history of MS who seek treatment for relapse must first be evaluated to rule out a worrisome acute trigger, and admission may be required for an identified systemic illness, infection, or other acute condition which is thought to have triggered the MS relapse. While patients initiated on IV steroids therapy will generally require admission for continued treatment, initiation and discharge home with high-dose oral prednisolone therapy is safe and effective. In these cases, the clinician should consider safety at home related to any neurologic disability brought on by the relapse, as well as management of pain and other symptoms.

When a new diagnosis of MS is suspected clinically or based on imaging results, further testing and treatment evaluation can often be performed as an outpatient, again assuming adequate mobility, home safety, and symptom control. Current consensus on quality standards for MS patients suggests that patients with new symptoms be referred to a neurologist within 4 weeks if not sooner. While often an achievable goal after ED discharge, hospital admission for advanced diagnostic testing and neurology consultation may be considered, particularly when access-to-care is a concern.

Foundations

Cerebral venous thrombosis (CVT) accounts for 0.5% to 1.0% of all strokes, often occurring in otherwise healthy young adults, though any age can be affected. The mean age at presentation is about 40 years, with the majority of cases (80%) presenting before the age of 50 years. Women are three times more commonly affected than men. Risk factors include thrombophilias (protein C and S deficiencies, factor V Leiden mutation), pregnancy and the post-partum period, oral contraceptives, infections of the head and neck, cancer, chronic inflammatory states, head trauma, and recent lumbar puncture or neurosurgical procedures. At least one risk factor is identified in 85% of patients, and multiple risk factors are found in 50% of patients.

CVT is caused by systemic or local imbalances in thrombotic and thrombolytic pathways, leading to thrombus formation in cerebral dural sinuses or veins. As the flow of venous blood from the brain is impeded, an increase in venous and capillary pressure occurs. Anastomoses of the cerebral venous system can initially compensate for increases in pressure, but when this capacity is overwhelmed a disruption of the blood-barrier occurs, leading to a decrease in cerebral perfusion pressure. This in turn, can lead to cerebral edema, infarction, and hemorrhage.

Clinical Features

There are four major CVT syndromes, which overlap in presentation and are detailed in Table 91.2 . The most common, isolated intracranial hypertension, typically presents with headache. Headache from CVT will often be described as localized, persistent or gradually worsening, though it may also be sudden, diffuse and severe, mimicking subarachnoid hemorrhage. Decreased visual acuity and papilledema may also result. Headache may worsen with transient increases in intracranial pressure (coughing, Valsalva). The second and third syndromes, focal neurologic deficits and seizures, are each found in approximately 30% to 40% of CVT cases. Motor weakness (which may be unilateral or bilateral) is the most common focal symptom, and aphasia may also be present. Sensory deficits are possible, though less common. Seizures may be focal or generalized and may present as status epilepticus. CVT should be considered in an at-risk patient presenting with both focal neurologic deficit and seizure. The final syndrome, encephalopathy, may present as altered mental status and confusion. This syndrome is less common and may be seen in more severe cases of thrombosis.