A Case of Longitudinally Extensive Transverse Myelitis

Primary CNS angiitis (PACNS) is distinguished from other vasculitides by its exclusive involvement of the CNS, generally in a multifocal manner. Lesions are typically, but not invariably, ischemic or hemorrhagic. Symptoms most frequently include headache, but also commonly involve cognitive impairment, focal neurological symptoms, and sometimes seizures. The disorder may involve medium or small-sized vessels. MRI of brain and spinal cord is usually abnormal, frequently showing cortical and subcortical infarcts. However, in the case of smaller vessel involvement, ischemic demyelination may be seen. Angiography frequently suggests the diagnosis by demonstration of “beading,” but biopsy is often necessary to firmly establish the diagnosis. Treatment is usually with high-dose pulse methylprednisolone followed by a prolonged course of oral prednisone, but the addition of other immunosuppressant medication is often necessary.

A Case of Personality Change and Seizure

The limbic encephalitides comprise a group of immune-mediated conditions that preferentially affect the limbic system, resulting in clinical manifestations such as memory deficits, seizures, and psychiatric disturbances. Limbic encephalitis (LE) may occur as a paraneoplastic syndrome related to underlying tumor, or as a primary autoimmune phenomenon. MRI often shows T2/FLAIR hyperintensities in the temporal lobe. CSF may be normal or may demonstrate mild lymphocytic pleocytosis and/or elevated protein. As the number of identifiable autoantibodies has rapidly increased in recent years, frequently one of these will be noted in the serum or spinal fluid. Antibodies to “classic paraneoplastic” intracellular antigens may only be markers of disease, given pathology studies demonstrating T cell infiltration, whereas antibodies to extracellular/cell membrane-associated antigens seem to be pathogenic and thus these tend to exhibit superior responses to immunotherapies. Treatment involves removal of the tumor if one is present, as well as various immunomodulatory therapies.

A Case of Fever and a Wrist Drop

Polyarteritis nodosa (PAN) is a systemic illness that most often involves the skin, kidneys, and gastrointestinal tract, in addition to the peripheral nervous system. It most often affects middle-aged individuals, men more than women. The particular type of peripheral neuropathy is often mononeuropathy or mononeuritis multiplex—a condition in which there is discrete involvement of multiple individual nerves. Definitive diagnosis of the vascular nature of the neuropathy requires peripheral nerve biopsy, which will demonstrate inflammation throughout the walls of small and medium-sized arteries. The CNS is also frequently involved in PAN. Constitutional symptoms, including fever, fatigue, and diffuse muscle and joint pain, are common and raise the suspicion of a systemic illness. Treatment generally involves the use of corticosteroids and immunosuppressive agents such as cyclophosphamide or azathioprine.

A Case of Myelitis with a Positive Anticardiolipin Antibody

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thromboembolic events and/or pregnancy morbidity in the setting of persistent antiphospholipid antibodies (aPL). APS may occur as a primary disorder or in the setting of underlying lupus. Common systemic manifestations include deep vein thrombosis and/or pulmonary embolism, livedo reticularis, thrombocytopenia, and fetal loss. The most common neurological consequence is stroke/transient ischemic attack (TIA) due either to in situ thrombosis or embolic disease. APS should be a primary consideration in a young patient with unexplained stroke/TIA. CNS abnormalities may occur in the absence of stroke, thought to be related to direct neuronal injury by aPL. Cognitive dysfunction is relatively common and has been shown to be associated with the presence of white matter lesions on MRI and livedo reticularis. T2 hyperintensities on MRI may be difficult to distinguish from those seen in multiple sclerosis. Less commonly reported neurological symptoms associated with aPL include chorea, transverse myelopathy, migraine, seizures, sensorineural hearing loss, and neuropsychiatric symptoms. Patients with stroke and persistent aPL should be treated with long-term anticoagulation. Select patients with other aPL-associated neurological syndromes may be treated with anticoagulation and/or immunomodulatory therapy on a case-by-case basis.

A Case of Monocular Blurred Vision

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system, typically affects young to middle-aged adults. Women are affected nearly three times as often as men. The diagnosis requires the demonstration of dissemination in space (DIS) and time (DIT) in a patient with no better clinical explanation. Evidence for either DIS or DIT or both may now be obtained from MRI, in addition to clinical manifestations. The most widely used diagnostic criteria are known as the McDonald criteria, and have been revised several times, most recently in 2017. In the current criteria, DIS may be achieved by the demonstration of at least one lesion in at least two different locations: periventricular, cortical/juxtacortical, infratentorial, or spinal cord. DIT may be considered in an initial magnetic resonance imaging (MRI) if there are simultaneously at least one gadolinium-enhancing lesion and one non-enhancing T2 hyperintense lesion; or alternatively, by the demonstration of a new lesion on any MRI subsequent to the first. The course of MS is characterized as relapsing-remitting (RRMS), secondary progressive, or primary progressive. Many effective disease-modifying agents are available for RRMS, but progressive forms have been much less successfully treated.

A Case of Cranial Neuropathies and Leptomeningeal Enhancement

IgG4-related disease is an immune-mediated fibroinflammatory syndrome that can affect nearly any organ system. Neurological involvement is uncommon. However, hypertrophic pachymeningitis, hypophysitis, and peripheral neuropathies have been described. Hypertrophic pachymeningitis may present with diffuse symptoms such as headache, cognitive changes, or seizure, as well as with focal symptoms dependent upon the involved anatomical location. Headache and multiple cranial neuropathies are the most common presenting features. Many patients have evidence of peripheral systemic disease at the time of presentation, and serum IgG4 levels are often elevated. A diagnosis of IgG4-related hypertrophic pachymeningitis is best made by exclusion of alternative diagnoses along with the presence of characteristic clinical, radiographic, and histological features. Biopsy is highly recommended. Immediate treatment is with high-dose corticosteroids to be tapered down over time. Steroid-sparing agents are often needed. Rituximab seems promising, but further research is needed.

The Unforgettable Encephalitis

Leucine-rich glioma-inactivated 1 (LGI1) limbic encephalitis is an autoimmune encephalitis characterized by subacute cognitive impairment, amnesia, seizures, faciobrachial dystonic seizures (FBDS), and hyponatremia. MRI of the brain typically demonstrates abnormal T2/FLAIR hyperintense signal in the mesial temporal lobe, hippocampal regions. CSF is surprisingly bland, and laboratory investigations often disclose a hyponatremia. Patients with LGI1 encephalitis generally respond to immunotherapies such as glucocorticoids, intravenous immunoglobulin (IVIg), and plasma exchange and steroid-sparing immunosuppressive agents. The etiology of LGI1 encephalitis can be either autoimmune or paraneoplastic, more commonly the former. Reported prognosis is favorable in about two-thirds of cases; however, some patients can relapse, and long-term outcome can be poor if diagnosis is delayed and residual memory impairment from hippocampal damage occurs.

Teratoma: “It’s Driving Me Crazy”

Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a severe, but often reversible, form of encephalitis associated with autoantibodies to the NR1–NR2 heteromers of the NMDA receptor. It is a paraneoplastic, immune-mediated condition predominantly affecting young women with ovarian teratomas. Encephalitis in the setting of an ovarian tumor should immediately raise suspicion for anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis, a paraneoplastic syndrome, which is typically underdiagnosed and can be fatal. Clinical presentation involves a prodromal viral-like illness, followed by neuropsychiatric disturbances, dysautonomia, seizures, dyskinetic movements, and potential progression to coma and possibly death. Early diagnosis and treatment with immunotherapy and tumor removal are instrumental in optimizing patient outcomes, as this is a potentially reversible condition.

Drowsiness and Double Vision

Bickerstaff brainstem encephalitis (BBE) is a syndrome defined by encephalopathy, ophthalmoplegia, and ataxia. It is associated with GQ1b antibodies, the same antibodies that are thought to be pathogenic in Miller-Fisher Syndrome (MFS). Thus, one may consider these syndromes as a continuum; the central nervous system is affected in BBE, while the peripheral nervous system is affected in MFS. BBE is an idiopathic autoimmune disorder that typically presents with acute to progressive cranial nerve dysfunction, usually ophthalmoplegia, associated with cerebellar ataxia, reflex abnormalities, and altered mental status, potentially progressing to coma. Bickerstaff first described this disorder in 1957, reporting eight patients with “brainstem encephalitis,” who presented with symptoms of drowsiness, acute ophthalmoplegia, ataxia, extensor plantar responses, and hemisensory loss. Prognosis for BBE is generally good, though patients may have a complicated course. The treatment options for BBE include intravenous immunoglobulin or plasmapheresis.

A Case of Cognitive Impairment and Ataxia

Celiac disease is an autoimmune enteropathy characterized by the presence of antigliadin antibodies and small intestinal mucosal injury, mediated by the adaptive immune system in response to gluten. Gastrointestinal symptoms typically include diarrhea, malabsorption/weight loss, and bloating/abdominal pain. Extra-intestinal symptoms often occur. The most commonly reported neurological syndromes are peripheral neuropathy, headache, and “gluten ataxia.” Gluten ataxia may occur in the setting of celiac disease or with non-celiac gluten sensitivity. Consistent with this being a cerebellar phenomenon, autopsy studies demonstrate inflammatory infiltration and Purkinje cell loss. Cerebellar atrophy as well as white matter abnormalities may be evident on MRI. Treatment is institution of a gluten-free diet. Intravenous immune globulin may also be helpful in select patients.