Sandip Shaunak

Treatment of refractory neurosarcoidosis with Infliximab

Background Neurological involvement in sarcoidosis is serious and often aggressive. Many patients respond to steroids but some show a progressive course despite treatment with steroids and even more potent immunosuppressive drugs. Objective The aim of this study was to describe our experience in the treatment of refractory neurosarcoidosis with Infliximab—its effect on the course of the disease and side effects. Methods A series of four patients are reported with neurosarcoidosis refractory to treatment with steroids combined with various immunosuppressive drugs in whom Infliximab was used. Results A good response, with improvement or stabilisation of the neurological condition, was seen in all cases, without significant side effects. Infliximab is a chimeric monoclonal antibody that neutralises the biological activity of tumour necrosis factor α, a cytokine thought to play an important role in the pathophysiology of sarcoidosis. Conclusion Our experience using Infliximab adds to the growing evidence that it may fulfil a useful role in cases of refractory neurosarcoidosis.

Leber’s hereditary optic neuropathy associated with multiple sclerosis: Harding’s syndrome

We describe a 32-year-old woman with sequential, severe, painless visual loss in one eye and then the other, and three temporally distinct episodes of neurological disturbance suggestive of demyelination in the spinal cord. She was positive for the T14484C mutation in the mitochondrial genome, one of three common mutations causing Leber’s hereditary optic neuropathy. In addition, MRI identified areas of demyelination within the periventricular white matter of the brain and within the spinal cord. The coexistence of multiple sclerosis and Leber’s hereditary optic neuropathy (Harding’s syndrome) is known to occur more often than would be expected by chance; therefore, screening for the Leber’s mutations in multiple sclerosis patients with severe visual loss should be considered because this has important prognostic and genetic implications.

Sporadic creutzfeldt-jakob disease presenting as progressive nonfluent aphasia with speech apraxia

Progressive non-fluent aphasia (PNFA) is typically associated with pathological changes consistent with frontotemporal lobar degeneration. A 65-year-old male presented with effortful speech, markedly impaired naming and features of speech apraxia, consistent with PNFA. Perceptuospatial function, calculation and executive function were intact. Brain SPECT showed left perisylvian hypoperfusion. He deteriorated profoundly over the subsequent eight months, with appearances on diffusion-weighted magnetic resonance imaging typical of sporadic Creutzfeldt-Jakob disease, which was confirmed pathologically at postmortem examination. While the presence of PNFA with speech apraxia is thought to predict underlying tauopathy, sporadic Creutzfeldt-Jakob disease may mimic this presentation and present in a highly circumscribed form not previously described.

Fulminant acephalgic giant cell arteritis with basal cerebral artery occlusion: A radiological and clinico-pathological study

A 60 year old man with no past history of note presented with a 5-week history of confusion and dysphasia of sudden onset. He denied any headaches or jaw claudication, but did report vague shoulder discomfort, which in retrospect was likely to reflect polymyalgia rheumatica. Clinical examination demonstrated a non-fluent dysphasia, subcortical cognitive impairment, unsteady gait and brisk reflexes. He was in sinus rhythm and had no carotid bruits, cardiac murmurs or stigmata of infective endocarditis. He had no vascular risk factors with the exception of a past history of smoking. Laboratory studies were significant for an erythrocyte sedimentation rate (ESR) of 66mm/hour and C-reactive protein (CRP) of 108mg/L. Brain magnetic resonance imaging (MRI) showed extensive ischaemic lesions involving the frontal and parieto-occipital regions (Figure 1(a)). Cerebrospinal fluid analysis and extensive vasculitis screening were normal or negative. Time of flight MR angiography suggested stenosis of the carotid and vertebral arteries at the point of dural entry into the skull base (Figure 1(b)). Catheter angiography confirmed severe stenosis of the internal carotid and vertebral arteries bilaterally at the point of dural penetration (Figure 1(c–f)). Echocardiogram was normal. Within 24 hours of admission, he developed jaw claudication although still had no headache. Giant cell arteritis (GCA) was suspected and he was pulsed with a 3-day course of intravenous methylprednisolone (1 g/day) followed by oral prednisolone 80mg/day. This led to a dramatic improvement in his jaw claudication and shoulder discomfort. A temporal artery biopsy performed within 1 week of steroid administration was negative. He was readmitted 25 days into the steroid treatment with increasing confusion and dysphasia. CRP was 17.5mg/L and ESR 8mm/hour. Repeat MRI brain showed multiple new internal border zone infarcts in the centrum semi-ovale (Figure 1 (g–i)) and also loss of flow void of the left internal carotid artery (Figure 1 (j)). MR angiogram confirmed new total occlusion of the left internal carotid artery at the skull base (Figure 1 (k, l)). He was treated for a presumptive diagnosis of fulminant GCA with a further 3-day course of intravenous methylprednisolone in addition to pulsed intravenous cyclophosphamide. He became increasingly encephalopathic and quadriplegic. A repeat MRI scan performed 3 weeks into cyclophosphamide treatment showed extensive new areas of cerebral infarctions in both centrum semi-ovale and right parieto-occipital lobes (Figure 2 (a, b)). A non-dominant frontal lobe biopsy showed areas of micro infarction without cerebral vasculitis or lymphoma. His condition deteriorated with new infarctions of the entire right cerebral hemisphere and the left anterior cerebral artery territory (Figure 2 (c, d)). He died 5 months into the illness. Post-mortem findings were consistent with GCA (Figure 2 (e–h)). GCA is a systemic granulomatous vasculitis of elderly individuals affecting large and medium sized vessels. The amount of elastic tissue in the artery dictates the site of GCA involvement, with the superficial temporal, vertebral, ophthalmic and posterior ciliary arteries being frequently involved in active GCA (1). Headache is the predominant symptom in more than two-thirds of patients but 7.5% of patients with biopsy proven ‘silent’ GCA manifest no headache (2). The headache is often non-specific, variable in intensity, character and location (2). Although the patient denied headache throughout the illness, one

A treatable cause for a painful movement disorder

A 44-year-old, right-handed woman presented with a 2 year history of intermittent burning and numbness over the left side of her face which had become continuous for the past 9 months. Over the past 7 months she had experienced spasms characterised by a sensation that the left side of her mouth was being pulled tight, associated with spontaneous flexed posturing of the left elbow and wrist with clawing of the hand. The spasms lasted for approximately 15 s and were extremely painful. They occurred in paroxysms lasting up to 2 h, several times a week. One month prior to presentation, she developed double vision on looking to the left with vertical separation of the images, and vertigo. She also reported fatigue, dry mouth and dry eyes over the previous 2 years. There was no previous medical history and she was taking no medications. Family history was unremarkable. Examination showed a markedly dry mouth. There was no skin rash or joint inflammation. On left lateral gaze the left eye deviated upwards in comparison with the right, a left hypertropia. Eye movements were otherwise normal. There was subjective reduction in sensation over the left side of the face in all trigeminal nerve divisions, consistent with a sensory trigeminal neuropathy, with preservation of the corneal reflex. Neurological examination was otherwise unremarkable. Routine biochemistry and haematology were normal. P and C antineutrophil cytoplasmic antibodies, rheumatoid factor, tissue autoantibodies, extractable nuclear antigen antibodies, anti-scl-70, anticentromere, antiphospholipid, anti-Jo1, anti-Ro, anti-La, anti-RNP and anti-Sm antibodies were all consistently negative. Antinuclear antibodies were slightly raised at a titre of 1 in 40 but double stranded DNA antibodies were negative. MRI of brain and cervical spine with contrast was normal. Lumbar puncture showed normal opening pressure, protein, glucose and cell count, and was negative for oligoclonal bands. Chest x …

1724 PCP prophylaxis in neurology – a review of the incidence of opportunistic infection in patients with myasthenia gravis

Opportunistic infections in neurology patients on long term immunosuppression are a rare but significant risk. Following three confirmed cases of pneumocysitis carinii pneumonia (PCP) in myasthenic patients on immunosuppression we undertook a review of the incidence of opportunistic infection requiring hospital admission in 62 patients with confirmed myasthenia gravis. 15% of myasthenic patients required hospital admission for treatment of opportunistic infection, community acquired pneumonia being the most common. Guidance exists for prophylaxis against PCP infection in non-HIV patients in both rheumatology and respiratory specialities. However, there is no formal guidance for neurology patients requiring long term immunosuppression. A cochrane review of randomised control trials of PCP prophylaxis in immunocompromised patients without HIV infection suggested that PCP prophylaxis is warranted in patients receiving 20 mg or more of prednisolone daily for at least one month who also have another cause of immunosuppression. Of our analysis of 62 patients with myasthenia gravis 94% received a course of prednisolone with 89% also receiving a steroid sparing agent. A significant number of patients remain on 20 mg prednisolone per day for at least one month and a co-prescribed steroid sparing agent (azathioprine, mycophenolate, ciclosporin or methotrexate). We aim to promote discussion amongst neurologists in their current practice regarding this topic.

PO248 Audit on efficacy of temporal artery biopsy (tab) for giant cell arteritis (gca) in lancashire teaching hospital nhs foundation trust

GCA is the commonest type of systemic vasculitis in patients above the age of 50 years. TAB is the cornerstone of diagnosis. In the right clinical setting, harvesting adequate TAB sample is crucial in making the correct diagnosis and for guiding treatment. Guidelines set by RCP on diagnosis and management of GCA (2010) as standard for this audit. A total of 148 TAB was carried out during that 5 year period. It was positive for arteritis in 37 (25%) cases and equivocal results in 3 (2%) cases. Inadequate sample was obtained in 3 (2%) cases. A repeat biopsy was carried out only in 4 (2.7%) cases, 2 for patients with inadequate samples. The mean sample size was 11.8 (range 6.1–17.5) mm. Minimum sample size was 3 mm (3 cases, 2%) and maximum sample size was 40 mm (1 case, 0.7%). In 43.2% cases the biopsy sample was greater than 10 mm (set minimum by RCP guidelines). This audit results suggest that in 56.1% cases the size of the TAB obtained were less than 10 mm (inadequate with risk of missing skip lesions). A trust policy to obtain at least 20 mm sample was made to improve diagnostic yield.

MITOCHONDRIAL CYTOPATHY PRESENTING WITH CEREBELLAR ATAXIA

A previously fit and well 59 year old man presented with a 3 year history of slowly progressive decline in mobility with increasing unsteadiness and falls. He also reported clumsiness of both hands and his wife noted poor memory. There was no family history of note, including deafness and diabetes. He drank alcohol occasionally. On examination he had signs consistent with a cerebellar and pyramidal syndrome with subcortical cognitive impairment. An MRI scan of the brain and spine showed significant generalised cerebral atrophy. CSF protein was 0.80g/L, with normal cell count and no oligoclonal bands. Blood tests were normal or negative for antineuronal antibodies, vitamin E, coeliac disease, autoimmune screen. Genetic tests for spinocerebellar ataxias, Freidreichs, fragile X syndrome and DRPLA were also negative. Muscle biopsy revealed mitochondrial aggregation with COX negative fibres, in keeping with a mitochondrial disorder. Genetic testing found a novel mtDNA variant (p.GLY46Asp) at low levels within the MT-CO3 gene. He has subsequently developed myoclonus and generalised tonic clonic seizures but there is no evidence of other system involvement. Mitochondrial disorders should be considered in the differential diagnosis of cerebellar ataxia, even in the absence of multisystem involvement or a significant family history.

A 9-YEAR RETROSPECTIVE STUDY ON CAVERNOUS SINUS SYNDROME

Background Cavernous sinus syndrome is caused by numerous diseases including vascular, infective, infiltrative, inflammatory, traumatic and thrombotic. Objective To determine the common presentation symptoms and signs, time period it takes to present and diagnose and the prevalence of the principal causes. Method A 9-year retrospective review (2002–2011) was performed on patients diagnosed with this syndrome at the Department of Neurology, Royal Preston Hospital, Lancashire Teaching Hospital. Results A total of 36 patients were identified (Age: 22–84 years). On average, first symptom to presentation was 12.6 months (Median 2.0). The commonest symptoms of presentation in sequential order were pain, double vision, visual impairment and ptosis. The commonest cranial nerves involved in chronological order were III, VI, V1, II, IV and V2. The average time from presentation to diagnosis was 1.3 months (Median 0.9). The cause was identified in 31 cases, with more than 50% being neoplastic, 29% inflammatory, 13% vascular and 6.5% infection. Six patients died and one patient is under palliative care. Conclusion Cavernous sinus syndrome is a serious disease with high morbidity and mortality. We describe a strikingly high prevalence of neoplasia in patients with cavernous sinus syndrome.