Variably protease-sensitive prionopathy in the UK: a retrospective review 1991-2008.

Variably protease-sensitive prionopathy is a newly described human prion disease of unknown aetiology lying out with the hitherto recognized phenotypic spectrum of Creutzfeldt-Jakob disease. Two cases that conform to the variably protease-sensitive prionopathy phenotype have been identified prospectively in the U.K. since the first description of the condition in 2008 in the U.S.A. To determine the incidence and phenotype of variably protease-sensitive prionopathy within a single well-defined cohort, we have conducted a retrospective review of patients referred to the National Creutzfeldt-Jakob Disease Research & Surveillance Unit during the period 1991-2008. The approach taken was to screen frozen brain tissue by western blotting for the form of protease-resistant prion protein that characterizes variably protease-sensitive prionopathy, followed by neuropathological and clinical review of candidate cases. Cases diagnosed as sporadic Creutzfeldt-Jakob disease with atypical neuropathology were also reviewed. Four hundred and sixty-five cases were screened biochemically, yielding four candidate cases of variably protease-sensitive prionopathy. One was discounted on pathological and clinical grounds, and one was a known case of variably protease-sensitive prionopathy previously reported, leaving two new cases, which were confirmed biochemically and neuropathologically as variably protease-sensitive prionopathy. A third new case that lacked frozen tissue was recognized retrospectively on neuropathological grounds alone. This means that five cases of variably protease-sensitive prionopathy have been identified (prospectively and retrospectively) during the surveillance period 1991-2011 in the U.K. Assuming ascertainment levels equivalent to that of other human prion diseases, these data indicate that variably protease-sensitive prionopathy is a rare phenotype within human prion diseases, which are themselves rare. Biochemical investigation indicates that the abnormal protease-resistant prion protein fragment that characterizes variably protease-sensitive prionopathy is detectable at low levels in some cases of sporadic Creutzfeldt-Jakob disease and conversely, that the form of abnormal prion protein that characterizes sporadic Creutzfeldt-Jakob disease can be found in certain brain regions of cases of variably protease-sensitive prionopathy, indicating molecular overlaps between these two disorders.

The Walton Centre neurology network - an equitable, sustainable and deliverable model for a large-scale neurology service.

UK neurology has many different models of provision and a shortage of essential clinical staff. Services are sometimes unsatisfactory and there is much variation and inequality, especially in areas outside London where there are far fewer consultants. Some hospitals have much better staffed and resourced neurological services than others which may have far less provision or even no neurology service at all. There is no national strategy or agreed model of service delivery - local areas have evolved individual arrangements, often dictated by consultant availability. We describe, with clear operational details, a neurology network model in a large population, with outcomes. In many areas with limited resources it could, by re-organisation of current services, be considered instead of existing separate, variable and potentially inequitable local arrangements.

Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts.

Although ribosomes are ubiquitous and essential for life, recent data indicate that monogenic causes of ribosomal dysfunction can confer a remarkable degree of specificity in terms of human disease phenotype. Box C/D small nucleolar RNAs (snoRNAs) are evolutionarily conserved non-protein-coding RNAs involved in ribosome biogenesis. Here we show that biallelic mutations in the gene SNORD118, encoding the box C/D snoRNA U8, cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts (LCC), presenting at any age from early childhood to late adulthood. These mutations affect U8 expression, processing and protein binding and thus implicate U8 as essential in cerebral vascular homeostasis.

A 10 year retrospective audit of long-term apomorphine use in Parkinson's disease.

OBJECTIVES: Apomorphine is a potent dopamine agonist useful in the treatment of Parkinson's disease patients with disabling motor fluctuations and 'off' periods, not responding to oral medication. It can also be of benefit in reducing dyskinesia by providing more constant dopaminergic stimulation and permitting lower levodopa dosage. However, there is a paucity of information on long-term benefits of apomorphine, including no large-scale phase III trial. We have examined our experience of apomorphine over the last 10 years, to assess indications, pattern of use, efficacy, and side effect profile. METHODS: All patients requiring apomorphine were identified through the Parkinson's disease Nurse Specialist's records. An audit form was produced so that the same information was gathered from all case-notes. RESULTS: There were 107 patients (61 males and 46 females). Mean age of disease onset was 50.9 years, SD+/-9.3 (range 29-78). The mean duration of disease at start of apomorphine treatment was 10 years (SD+/-4.8, range 2-29). The most common indications for apomorphine were severe unpredictable 'off' periods (75.7 %), motor fluctuations (18.7 %) and dyskinesia (5.6 %). Most patients (63.6 %) used both intermittent subcutaneous injections and infusion via pump; 25.2% were on intermittent injection, and 11.2 % infusion alone. Mean dose per injection was 3.7 mg. Mean infusion dose 69.8 mg, running over a mean of 13.5 hours. The mean duration of intermittent apomorphine use was 48.2 months. The mean duration of infusion was 25.1 months. Complications included skin problems in 16 patients, 2 had symptomatic hypotension, 2 worsening confusion, 1 new confusion and 5 new hallucinations (after sometime on apomorphine). Sixteen patients have stopped using apomorphine completely. Thirteen have stopped the pump, but continue on intermittent injections. CONCLUSION: Subcutaneous apomorphine is easy for patients to use, is well tolerated and has a low incidence of side effects, especially confusion.

Spontaneous CSF Collection in the Cervical Spine may Cause Neurological Deficit and Intra-cranial Hypotension.

OBJECTIVE: a case is described of a spontaneously occurring cerebrospinal fluid collection in the ventral cervical spine which caused radiculopathy and spontaneous intracranial hypotension. CASE: a sixty eight year old Caucasian man presented with a 2 year history of proximal upper limb weakness with a his-tory of trivial cervical trauma many years previously. METHODS: the patient was investigated with blood tests for causes of peripheral neuropathy, nerve conduction and electro-myography studies, lumbar puncture and MRI of the brain and spine with contrast. RESULTS: a cerebrospinal fluid collection was identified in the ventral cervical spinal cord causing mass effect associated with cord atrophy and there were signs of spontaneous intracranial hypotension on the MRI brain including subdural cere-brospinal fluid collections, meningeal enhancement and slumped posterior fossa. CONCLUSIONS: this is the first description of a spontaneous spinal fluid collection causing direct compression and cord sig-nal change, manifest as a motor deficit, with intracranial signs of spontaneous hypotension. Spinal imaging is recom-mended in cases of spontaneous intracranial hypotension and cerebrospinal fluid collections in the spine may rarely be a cause of radiculopathy in such cases.

Cannabis-induced propriospinal myoclonus.

We report on a case of a 25-year-old woman with clusters of myoclonus induced by a single exposure to inhaled cannabis. Investigations excluded a structural abnormality of the spine. Multi-channel surface EMG with parallel frontal EEG recording confirmed the diagnosis of propriospinal myoclonus.