Late-onset Leber's hereditary optic neuropathy presenting with longitudinally extensive myelitis harbouring the m.14484T>C mutation: Extending the genotype-phenotype spectrum.

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease leading to visual loss, typically in young men, and rarely displays extra-ocular manifestations including spinal cord disease. We report the case of a 57-year-old man who presented with a longitudinally extensive dorsal column lesion as the first manifestation of LHON, with the onset of bilateral progressive optic neuropathy 11 months later, harbouring the m.14484T>C mutation. To our knowledge this is the most extensive cord lesion preceding optic neuropathy traversing the cervical and thoracic cord. We review the literature of all published cases of LHON in which spinal cord involvement was the presenting feature of the disease, summarising the clinical phenotype, demographics, radiological characteristics and genotype. We highlight the importance for diagnostic vigilance in patients with either longitudinally extensive dorsal column myelopathy, optic neuropathy or both.

Bickerstaff's brainstem encephalitis associated with anti-GM1 and anti-GD1a antibodies.

Bickerstaff's brainstem encephalitis (BBE) is a Guillain-Barré syndrome (GBS) spectrum disorder associated with predominantly central nervous system predilection. Patients exhibit a variable constellation of depressed consciousness, bilateral external ophthalmoplegia, ataxia and long tract signs. Although the pathophysiology is not fully understood, it has been associated with anti-GQ1b antibodies in two-thirds of patients. We present a patient with clinical features consistent with BBE and positive anti-GM1 and anti-GD1a antibodies. A diagnostic approach to the acutely unwell patient with brainstem encephalitis is explored in this clinical context with a literature review of the aforementioned ganglioside antibody significance. Intravenous immunoglobulin therapy is highlighted in BBE using up-to-date evidence-based extrapolation from GBS.

Blurred vision and pain in the eye.

Subacute unilateral visual impairment accompanied by pain on eye movement is characteristic of optic neuritis. Most cases of optic neuritis resolve spontaneously, and acute treatment with intravenous steroids hastens recovery but does not alter the ultimate visual outcome. Brain magnetic resonance imaging (MRI) may permit a diagnosis of multiple sclerosis (MS) to be made after a single clinical demyelinating event such as optic neuritis. Current evidence supports the introduction of disease-modifying therapy in patients with a single clinical event such as optic neuritis and brain MRI compatible with MS. The diagnosis of MS is a confronting life event associated with significant personal, social and financial burdens. The diagnosing neurologist should provide a detailed explanation of the disease and its clinical spectrum and introduce the patient to the wide range of support services, educational material and MS clinics.

Variant Creutzfeldt-Jakob disease in a transfusion recipient: coincidence or cause?

BACKGROUND: To date there have been four instances of infection transmitted through blood transfusions derived from individuals who later developed variant Creutzfeldt-Jakob disease (vCJD). The identification of further transmission of vCJD through this route would have important implications for risk assessment and public health. STUDY DESIGN AND METHODS: Through the UK Transfusion Medicine Epidemiology Review (TMER) the fate of blood donations from individuals who develop vCJD is traced and recipients of labile components are identified. The details of recipients are cross-checked with the register of vCJD cases held at the National CJD Surveillance Unit (NCJDSU) to identify any linkage between donors and recipients. In the reverse study, when individuals with vCJD are found to have a history of blood transfusion the donors of the transfused blood components are traced and their details cross-checked with the vCJD register to identify any missed or unrecognized linkage between donors and recipients. CASE REPORT: A case of vCJD has been identified with a history of blood transfusion in infancy. The donors who provided the components transfused cannot be identified, but a blood donor known to have donated blood to another individual who subsequently developed vCJD could have been a donor to the index case. RESULTS: The at-risk donor is alive 20 years after the relevant donation and continued to donate for some years, until identified as at risk, with 27 other blood components issued for use in patients, none of whom are known to have developed vCJD. CONCLUSION: Circumstantial evidence has raised the possibility that the case in this report represents a further instance of transfusion transmission of vCJD. However, detailed investigation indicates that the pattern of events may have occurred by chance and disease in this individual may have been caused by transmission of bovine spongiform encephalopathy infection, as is the presumed cause in other primary cases of vCJD.

Variant Creutzfeldt-Jakob disease: neuropsychological profile in an extended series of cases.

Neuropsychological data on an extended series of cases of variant Creutzfeldt-Jakob Disease (vCJD) are presented, complementing earlier findings from smaller sample studies of this condition. Distinct neuropsychological features in this extended series included relatively preserved verbal knowledge, immediate verbal memory span, and elementary visual processing. This sparing contrasted with ubiquitous impairment in every vCJD patient on timed tests of verbal fluency and digit-symbol substitution. There were also high rates of impairment on tests of memory, and of visuoperceptual and visuospatial reasoning. Our findings lend support to the view that distinctive neuropsychological features may be one of the diagnostic markers of the condition.

The role of cerebrospinal fluid proteins as early diagnostic markers for sporadic Creutzfeldt-Jakob disease.

The utility of cerebrospinal fluid (CSF) proteins such as 14-3-3, tau protein and S-100b as diagnostic markers in the early stages of sporadic Creutzfeldt-Jakob disease (sCJD) is unclear. We examined the diagnostic value of these CSF proteins in the early stages of sCJD (within 6 weeks of onset of symptoms). Four groups of patients were compared: patients with probable or neuropathologically confirmed sCJD with CSF taken within 6 weeks of onset ('sCJD<6-week group', n=47); patients with CSF taken within 6 weeks of disease onset but with a diagnosis other than CJD ('non-sCJD<6-week group', n=21); patients with neuropathologically proven sCJD where CSF was taken later than 6 weeks after onset ('sCJD>6-week group', n=206); patients with CSF taken later than 6 weeks after onset of symptoms but with a diagnosis other than CJD ('non-sCJD>6-week group', n=166). The sensitivity and specificity of different combinations of neuronal proteins were ascertained. The sensitivities of all three markers were similar and ranged from 96% to 98%. The sensitivity of these markers was greater in the 'sCJD<6-week group' than in the 'sCJD>6-week group'. This may be due to differences in the PRNP codon 129 and PrP isotype distribution between these groups. CSF tau protein had the greatest specificity (82%). We found all three CSF protein markers to be highly sensitive in the early stages of sCJD, with CSF tau protein having the greatest specificity and efficiency. Our findings indicate that CSF protein markers are effective tests in the early stages of sCJD.

Cytomegalovirus papillitis in an immunocompetent patient.

A 22-year-old immunocompetent woman who presented with a 3-week history of fever, headache, and visual loss and was found to have subnormal visual acuity and bilateral optic disc swelling. Serum cytomegalovirus (CMV) IgM and IgG and polymerase chain reaction results were positive, indicating an acute CMV infection. No cause of immunocompromise was found. After treatment with intravenous ganciclovir, the papillitis and systemic CMV illness resolved with no residual deficit. This is the first reported case of primary CMV papillitis to be successfully treated with ganciclovir alone.

A case of celiac disease mimicking amyotrophic lateral sclerosis.

BACKGROUND: A 44-year-old male presented to a general neurology clinic with a 6-month history of progressive right-sided spastic hemiparesis without sensory symptoms or signs. The thigh muscle in the affected leg showed signs of wasting. The patient had a remote family history of celiac disease. INVESTIGATIONS: Neurological examination, neurophysiological studies, brain MRI scan, routine blood tests, duodenal biopsy, cerebrospinal fluid analysis including polymerase chain reaction test for JC virus DNA, serological testing for HIV and for the presence of serum antibodies to endomysium, gliadin and tissue transglutaminase. DIAGNOSIS: Celiac disease with neurological involvement, mimicking amyotrophic lateral sclerosis. MANAGEMENT: Strict gluten-free diet.