Granulomatous inflammatory myopathy associated with myasthenia gravis. A case report and review of the literature.

A 76-year-old woman with a history of granulomatous pulmonary disease presented with myasthenia gravis involving ocular, pharyngeal, and proximal extremity weakness. She responded to prednisone therapy but three years later developed predominantly distal appendicular weakness. Reinvestigation demonstrated a granulomatous inflammatory myopathy.

Familial autoimmune myasthenia gravis and thymoma: occurrence in two brothers.

At ages 31 and 42 years, two brothers presented with clinical, pharmacologic, electrophysiologic, and immunologic characteristics of autoimmune myasthenia gravis. At thymectomy, both had histologic findings of epithelial thymoma. HLA analysis revealed A2, A3, B7, and B39 antigens in one patient and A3, A24, B7, and B40 antigens in the other. Familial myasthenia gravis with thymoma has not been described previously. Familial thymoma has been rarely reported, but never with myasthenia gravis.

Postpartum intracranial venous thrombosis associated with dysfunctional protein C and deficiency of protein S.

Development of intracranial dural sinus thrombosis in the postpartum period has been attributed to the hypercoagulable state of pregnancy. With increasing recognition of the role of the vitamin K-dependent proteins, protein C and protein S, in intracranial venous and arterial thrombotic events, our understanding of the cause of thrombotic events has improved. We report a patient who developed a superior sagittal sinus thrombosis in the second week postpartum, associated with a dysfunctional protein C and a decreased free protein S concentration.

Subacute sclerosing panencephalitis manifesting as viral retinitis: clinical and histopathologic findings.

PURPOSE AND METHODS: To describe the clinical and histopathologic features of a patient with viral retinitis secondary to subacute sclerosing panencephalitis. RESULTS: The patient was a human immunodeficiency virus-negative intravenous drug abuser with an acute retinitis that later progressed to encephalitis despite aggressive treatment for possible viral, protozoal, bacterial, and rickettsial infections. The patient had many of the characteristic findings of subacute sclerosing panencephalitis, including a history of measles in early childhood, myoclonus, periodic complexes on electroencephalographic testing, persistently elevated serum and cerebrospinal fluid antimeasles immunoglobulin G (IgG) titers, and a cerebrospinal fluid oligoclonal IgG gammopathy. Ultrastructural examination demonstrated numerous filamentous microtubular intranuclear viral inclusions in the nuclear layers of the retina consistent with the measles virus. This case is unusual in that our patient developed subacute sclerosing panencephalitis later in life and because there was an 8-year period between presumed viral infections in the two eyes. CONCLUSIONS: An acute retinitis in an intravenous drug abuser is not always caused by human immunodeficiency virus-related infections; not all viral retinitis responds to therapy; and mortality as well as the usual morbidity may be associated with viral retinitis. One might consider the diagnosis of subacute sclerosing panencephalitis in a young person with an acute retinitis with little or no vitreal inflammation and lack of response to anticytomegalovirus and antitoxoplasmosis therapy.

Treatment of dural sinus thrombosis with local urokinase infusion. Case report.

Current therapy for dural sinus thrombosis consists of supportive measures, anticoagulation therapy, and in some cases intravenous infusion of a fibrinolytic agent. A patient with extensive dural sinus thrombosis was successfully treated with local urokinase infusion. The technique and rationale for this aggressive therapy are discussed.

The spectrum of neuroimaging abnormalities in solvent abuse and their clinical correlation.

The brain magnetic resonance (MR) images and medical records of 6 patients with a history of chronic toluene abuse were reviewed retrospectively. The imaging findings were correlated with clinical impairment. The major findings consisted of atrophy (6 patients), white matter T2 hyperintensity (6 patients), and T2 hypointensity involving the basal ganglia and thalami (5 patients). Also seen was focal enhancement, previously unreported for patients who abused toluene. This study showed a correlation between the degree of neurological impairment and extent of white matter disease. There was no correlation between the severity of white matter changes on MR images and the presence of T2 hypointensity or duration of toluene abuse. There was no definite clinical evidence of damage to the basal ganglia and thalami despite the MR imaging finding of T2 hypointensity. Temporal evidence against the theory that toluene accumulation causes the T2 hypointensity was found.

Primary intravascular lymphomatosis associated with Mycobacterium marinum.

Intravascular lymphomatosis (i.v.l.) is a rare condition in which neoplastic cells preferentially infiltrate blood vessels of the central nervous system. Nonspecific symptoms associated with i.v.l. include dementia, seizures, and multifocal cerebrovascular events. i.v.l. was discovered at autopsy of a patient whose neurological deficits were predated by a particularly aggressive form of Mycobacterium marinum soft-tissue infection. It is speculated that i.v.l. may have had an occult effect on the patient's cell-mediated immunity that predisposed him to this normally innocuous mycobacteria.

Sarcoid myelopathy.

A 45-year-old woman with history of iritis, uveitis, and sarcoidosis of the skin presented with a subacute cervical myelopathy. Magnetic resonance imaging (MRI) showed patchy, multifocal, gadolinium-enhancing intramedullary lesions of the spinal cord, and extramedullary lesions of the basal cisterns and fourth ventricle. Symptoms and MRI abnormalities were improved within 1 month of corticosteroid therapy.

The history of myasthenia gravis.

The first case of myasthenia gravis (MG) was described in 1672. Treatment of MG was negligible until Mary Walker's seminal observation in 1934 of improvement with physostigmine and neostigmine injections. Blalock reported the initial success with thymectomy around 1940. Edrophonium was introduced around 1950 and pyridostigmine in the mid-1950s. John Simpson's hypothesis of an autoimmune etiology for MG in 1960 was later proven correct, and subsequent use of immunosuppressive therapy including corticosteroids led to the modern era in management of MG.

Acute peripheral neuropathy in adults. Guillain-Barré syndrome and related disorders.

Acute paralysis in adults has an extensive assortment of etiologies. Guillian-Barré syndrome is the most common cause of acute neuropathy in adults. This review emphasizes pathophysiology, clinical features, differential diagnosis, and a practical approach to the laboratory work-up for patients with suspected Guillian-Barré syndrome. The current status of immunotherapy is reviewed.

Reversible cortical blindness (Anton's syndrome) associated with bilateral occipital EEG abnormalities.

A 50-year-old woman with systemic lupus erythematosus was admitted in an obtunded state. An EEG recorded while she was unconscious demonstrated one episode of rhythmic sharp wave activity in the left occipital area that lasted for 5 minutes and was followed later in the same recording by an episode of high amplitude sharp wave discharges in the right posterior temporal and occipital areas. When the patient regained consciousness, she had an Anton's syndrome of cortical blindness with denial. When she recovered light perception only, the EEG demonstrated synchronous and independent right and left occipital-posterior temporal periodic lateralized epileptiform discharges (PLEDs). Cortical blindness (Anton's syndrome) associated with abnormal electrical activity in the occipital areas has only rarely been reported. Our case is significant for the following reasons: 1) PLEDs maximal right and left occipital areas associated with bilateral visual loss has not previously been observed; 2) abnormal electrical activity in the occipital lobes may be a reversible cause of Anton's syndrome.

Lymphorrhage localized to the muscle end-plate in myasthenia gravis.

Lymphocytic infiltration of muscle (lymphorrhage) is occasionally observed in myasthenia gravis. We describe a 56-year-old woman with autoimmune myasthenia gravis, whose muscle biopsy specimen demonstrates acute cellular reaction localized to the end-plate region. This observation raises the possibility of a more direct role of the cellular immune system in the pathogenesis of the disease, and provides a morphologic link between the human and the experimental myasthenia gravis.

Caffeic acid phenethyl ester extends survival of a mouse model of amyotrophic lateral sclerosis.

There is currently very limited effective pharmacological treatment for amyotrophic lateral sclerosis. Recent evidence suggests that caffeic acid phenethyl ester has strong anti-inflammatory, anti-oxidative, and anti-neuronal death properties; thus, the present study tested the effects of caffeic acid phenethyl ester in mice expressing a mutant superoxide dismutase (SOD1(G93A)) linked to human amyotrophic lateral sclerosis. Administration of caffeic acid phenethyl ester after symptom onset significantly increased the post-onset survival and lifespan of SOD1(G93A) mice. Moreover, immunohistochemical analysis detected less activation of microglia and astrocytes and higher motor neuron counts at an early symptomatic stage (7 days following onset) in the spinal cords of SOD1(G93A) mice given caffeic acid phenethyl ester treatment. Additionally, lower levels of phosphorylated p38, a mitogen-activated protein kinase that is involved in both inflammation and neuronal death, were observed in the spinal cords of SOD1(G93A) mice treated with caffeic acid phenethyl ester for 7 days. These results indicate that caffeic acid phenethyl ester may represent a novel and effective therapeutic for the treatment of amyotrophic lateral sclerosis, and these significant neuroprotective effects observed in a commonly used amyotrophic lateral sclerosis mouse model validate the therapeutic potential of caffeic acid phenethyl ester for slowing disease progression by attenuating the neuroinflammation and motor neuron cell death associated with clinical amyotrophic lateral sclerosis pathology.

Trends in American Board of Psychiatry and Neurology specialties and neurologic subspecialties.

OBJECTIVE: To review the current status and recent trends in the American Board of Psychiatry and Neurology (ABPN) specialties and neurologic subspecialties and discuss the implications of those trends for subspecialty viability. METHODS: Data on numbers of residency and fellowship programs and graduates and ABPN certification candidates and diplomates were drawn from several sources, including ABPN records, Web sites of the Accreditation Council for Graduate Medical Education and the American Medical Association, and the annual medical education issues of the Journal of the American Medical Association. RESULTS: About four-fifths of neurology graduates pursue fellowship training. While most recent neurology and child neurology graduates attempt to become certified by the ABPN, many clinical neurophysiologists elect not to do so. There appears to have been little interest in establishing fellowships in neurodevelopmental disabilities. The pass rate for fellowship graduates is equivalent to that for the "grandfathers" in clinical neurophysiology. Lower percentages of clinical neurophysiologists than specialists participate in maintenance of certification, and maintenance of certification pass rates are high. CONCLUSION: The initial enthusiastic interest in training and certification in some of the ABPN neurologic subspecialties appears to have slowed, and the long-term viability of those subspecialties will depend upon the answers to a number of complicated social, economic, and political questions in the new health care era.

Subcutaneous IGF-1 is not beneficial in 2-year ALS trial.

BACKGROUND: Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS. METHODS: A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used. RESULTS: There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period. CONCLUSIONS: Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis.

Pearls and pitfalls in the diagnosis and management of neuromuscular junction disorders.

Myasthenia gravis (MG) is a common autoimmune disorder characterized by the presence of pathogenic antibodies directed against the acetylcholine receptor. Patients present with variable degrees and distribution of fluctuating weakness, at times life-threatening. Clinical manifestations, establishment of diagnosis, the natural history of MG, and therapeutic options are herein reviewed with an emphasis on pearls and pitfalls of clinical relevance. Far less common is Lambert-Eaton syndrome (the myasthenic syndrome), another autoimmune disorder due to the presence of antibodies directed against the PQ-type voltage-gated calcium channels. Clinical features and treatment issues of these and other disorders of neuromuscular transmission are reviewed.

Pearls and pitfalls in the horror cinema.

Observations on the neurologic signs and symptoms of Count Dracula, Wolfman, and Frankenstein's Monster are presented as viewed by a specialist in neuromuscular disease. Key clinical features of these horror movie figures illustrate a variety of pearls in the diagnosis of a variety of neurologic disorders, including porphyria, lead poisoning, osteosclerotic myeloma, and myasthenia gravis.

Blinded and seeing the light, (John Noseworthy), Lou Gehrig and other tales of enlightenment).

Patients having serious neurological diseases often wonder why clinical trials must use controls and double blinding in order to prove efficacy. Studies on the effect of examiner blinding in multiple sclerosis trials, as well as the published results of an unblinded uncontrolled clinical trial of Vitamin E therapy in patients with amyotrophic lateral sclerosis (including Lou Gehrig) provide clear illustrations of the impact of blinding and controls on outcome. These reports serve as a resource for physicians, patients and their families in discussing the rationale for controls and double blinding, and instill caution that should be used when judging results of studies which are unblinded or uncontrolled.