Anisha Doshi

A CASE SUPPORTING THE ROLE OF THE CEREBELLUM IN DYSTONIA

A 28 year old right handed man presented with a ten year history of difficulty in writing. He had been prescribed metoclopramide for an episode of vomiting one week prior to this and had been admitted for an acute dystonic reaction with oculogyric crisis. He had difficulty gripping the pen, his writing was untidy and he pressed excessively on the paper. Over the next year, involuntary movements developed, including posturing of the right arm and right foot particularly on action, and fine tasks, such as doing up buttons, were impaired. Examination showed dystonic posturing of the right foot on running, writers cramp and finger/nose ataxia on the right. Magnetic resonance imaging revealed a large arteriovenous malformation (AVM) in the right cerebellar hemisphere extending into the pons. Formal arteriography confirmed a large high flow AVM with a large vein draining in the torcular with a preceding stenosis. Dystonia is a hyperkinetic movement disorder characterised by involuntary sustained muscle spasms and posturing. Secondary dystonia has many causes including structural lesions of the basal ganglia, particularly the putamen. This case illustrates right sided dystonia and upper limb ataxia ipsilateral to a large cerebellar AVM and adds to the emerging literature for the role of the cerebellum in dystonia. Stimulation of deep cerebellar regions in humans can result in tonic posturing of the neck and limbs. Brainstem lesions causing dystonia have been reported and have implicated cerebellar pathways in the pathophysiology. Diffusion tensor imaging has indicated that in DYT1 and DYT6 mutations there are dorsal pontine microstructural abnormalities in the superior cerebellar peduncle, implicating cerebello–thalamo–cortical pathways in dystonia pathogenesis. A study of patients with primary focal dystonia indicated delayed eyeblink conditioning compared to controls which is an experimental paradigm dependent on the cerebellum. This provides indirect neurophysiological evidence of olivo–cerebellar pathway changes in these patients. However, in primary dystonia there is absence of cerebellar clinical examination signs which may indicate a compensatory role of the cerebellum. It is unclear whether all manifestations of dystonia involve both basal ganglia and cerebellar circuitry, or whether there is a spectrum ranging from pure cerebellar dystonia, overlapping basal ganglia and cerebellar dystonia, and pure basal ganglia dystonia. There is evidence in from many experiments to support a role for the cerebellum in the pathogenesis of dystonia. Our case adds to the literature. The key area that needs clarification is whether the cerebellar outflow abnormality causing dystonia is stimulatory or inhibitory role. Figure 1: T2 weighted Magnetic Resonance Imaging showing a large arteriovenous malformation in the right cerebellar hemisphere extending into the pons.

REGIONAL EFFICACY OF NATALIZUMAB TREATMENT IN RELAPSING-REMITTING MULTIPLE SCLEROSIS (RRMS)

Natalizumab is an established treatment for highly active Relapsing-Remitting Multiple Sclerosis (RRMS). Two-year efficacy in the AFFIRM trial showed No Evidence of Disease Activity(NEDA) – no relapses, no disability progression, no new MRI lesions – in 37% of patients compared with 7% in the placebo group. NEDA is increasingly used as a treatment goal in RRMS. Methodology We performed a retrospective analysis of Natalizumab treatment in RRMS patients in our centre. We assessed the proportion of patients achieving NEDA in a typical clinical setting with at least 1 year treatment duration and analysed for predictors of response. Results Mean age was 41.44 (13–62), 77% (51) of patients were female. 56 out of 66 patients had been on Natalizumab for >1year and were analysed. 55.36% patients achieved NEDA at 1 year. No statistically significant predictors (age, gender, starting disability and relapse rate) of response were identified. Discussion The data confirms in a typical UK clinical setting good treatment response was achieved in highly active RRMS patients using Natalizumab. No additional factors were found which could predict treatment response suggesting within the limitations of power and length of this study that Natalizumab is effective in a broad range of highly active RRMS patients.

BING-NEEL SYNDROME: A RARE CAUSE OF PROGRESSIVE GAIT DISTURBANCE AND DEMENTIA

A 69 year old retired lady presented with a 3 year history of progressive gait disturbance with unsteadiness and falls. Over the preceding year she had become recluse, failing to attend social gatherings and becoming anxious. She complained of lethargy and poor appetite and had lost weight. A witnessed generalised seizure led to admission. Examination revealed mixed pyramidal and extrapyramidal signs in the limbs with global hyperreflexia and upgoing plantars. There was upper limb ataxia with bilateral intention tremor and myoclonus. She was only obeying one stage commands. Investigations revealed elevated ESR and monoclonal IgM kappa band with paraprotein concentration 9.4 g/L. MRI whole axis revealed periventricular diffuse T2 and FLAIR signal change and prominence of the leptomeninges along the distal spinal cord, conus medullaris and cauda equina. Bone scan showed prominent uptake within both humeri. Bone marrow trephine biopsy indicated a low-grade B-cell lymphoproliferative disorder; lymphoplasmacytic lymphoma. Serial CSF analysis revealed lymphocytic pleocytosis with elevated protein of 4.47–6.25 g/L. CSF protein electrophoresis demonstrated the presence of an IgM paraprotein with monoclonal IgM kappa band on immunonofixation. CSF immunophenotyping confirmed the presence of clonal B–cells. We therefore present a rare case of Bing-Neel Syndrome, CNS manifestation of Wäldenstroms Macroglobulinaemia.

JUST A GRAZE

We describe a case of a diagnostically difficult stroke mimic, cephalic tetanus.1 Currently there are 12–15 cases of tetanus reported annually in the United Kingdom,2 but worldwide it accounts for one million deaths, 80% being in Africa and South East Asia.3 Tetanus is caused by infection with clostridium tetani.4 5 Cephalic Tetanus is defined as a combination of trismus and paralysis of one or more cranial nerves, most commonly the facial nerve. It is rare, 0.9–3% of all tetanus cases, and has a high mortality of between 15–30% if it progresses to generalised tetanus.1 A 76 year old right handed lady presented to the stroke unit with sudden onset of swallowing difficulty, speech impairment and left sided facial weakness on waking. She had multiple vascular risk factors, however on examination her signs had resolved. Of note she had a sutured right supraorbital laceration sustained a week prior to presentation following a road traffic accident. Computed tomography (CT) showed no acute stroke and confirmed the presence of a large supraorbital haematoma. She was treated with a combination of high dose aspirin and prednisolone therapy for a presumed left sided transient ischaemic attack and a right sided Bells palsy. During the next few days the patient had labile blood pressure and heart rate readings, complained of difficulty opening her jaw, and had intermittent episodes of laryngeal episodes. Her admission CT was reviewed and note was made of a 3 mm metallic fragment and locules of gas within her haematoma. A clinical diagnosis of cephalic tetanus was made and this was later confirmed on wound culture isolates. As highlighted by our case, ptosis and cranial nerve palsies may precede trismus in cephalic tetanus, and only two published case reports in Korea describe this order of presentation worldwide.1 The spore–forming motile gram positive bacillus Clostridium tetani4 5 is rarely isolated and therefore the diagnosis is clinical. Two toxins are produced; Tetanolysin which damages surrounding viable tissue, and Tetanospasmin which inhibits GABA and glycine presynaptic release leading to the clinical syndrome of: rigidity, muscle spasms and autonomic dysfunction.3 Management is based on three principles; preventing further toxin release with debridement and antibiotics, neutralising toxin present outside of the Central Nervous System (CNS) with tetanus immunoglobulin, and minimising the effects of the toxins in the CNS with early anaesthetic support.4 5 All patients require full tetanus toxoid immunisation post–infection.1 5 In conclusion, when approaching a patient with head injury and one or more cranial nerve palsies, it is important to consider cephalic tetanus. Figure 1 Axial CT head shows a large subcutaneous haematoma overlying the right frontal convexity with locules of gas and a 3mm metallic density at its inferior aspect, possibly representing a foreign body.

AN UNUSUAL BUMP ON THE HEAD: INTRAEXTRACRANIAL MENINGIOMA PRESENTING INCIDENTALLY

An 82–year–old gentleman presented to hospital following a fall. The patient had no recollection of the fall, and was found conscious sometime later on the floor by the neighbours. At the time of assessment, it was noted that the patient had a large swelling over the frontal area of his scalp, but the duration of this sign was unclear. Positive findings on examination included; brisk lower limb reflexes, an unsteady gait, and speech disinhibition. His cognition was more formally assessed; executive testing of frontal lobe function demonstrated good fluency with word and number–letter tasks but reduced design fluency. There was no evidence of frontal release signs, and no impulsivity. The patient displayed minimally impaired echopraxia, imitation behaviour and some counting task difficulties. CT head revealed a lesion in both frontal lobes with extracranial extension. MRI revealed a 10 cm mass with an intracranial and extracranial component that was composed of solid material which enhanced with contrast (figure 1). The skull itself was preserved but did show some lytic lesions. A chest X–ray revealed no focal lesions. Subgaleal biopsies showed two collagenous tissue fragments infi ltrated by solid synctial sheets of a cellular neoplasm that in places form perivascular aggregates. There was mild pleomorphism, with oval nuclei vesicular comprising a single prominent nucleolus. The mitotic activity in the small tumour fragments was inconspicuous and there was no necrosis. There was diffuse strong immunoreactivity for epithelial membrane antigen in keeping with a neoplasm of meningothelial origin. Overall this was an intracranial meningioma with extra cranial spread into the subcutaneous tissue of the scalp. Due to minimal symptomatology the patient was managed conservatively and was discharged home. Meningiomas are common intracranial neoplasms, accounting for 18% of all primary brain tumours.1 Extracranial manifestations however, are rare with an incidence of 1% to 2%.2 Analysis from a French neurosurgical unit between 1982 and 1993 revealed 11 cases of intra–extracranial vault meningiomas with six cases originating in the frontal areaas in our case.3 Cutaneous locations of extracranial meningiomas are the most common, followed in descending order by orbital, paranasal, temporal and oral presentations.1 10 years between onset of symptoms and diagnosis of meningioma is not uncommon.3 Hoye et al hypothesised four aetiological ways in which extracranial meningiomas may develop;4  1. Primary intracranial meningioma with extracranial extension (secondary)  2. From arachnid cell rests, accompanying cranial nerve sheaths through a neural foramen (primary)  3. Ectopic, from extracranial embryonic arachnoid cell rests (primary)  4. Metastases from intracranial meningiomas (secondary). This is very rare with Teague et al reporting a metastatic meningioma within the lung.5 We conclude that our patients extracranial extension was probably due to trans diploic spread. The intracranial veins (including the diploic veins which communicate with the dural sinuses) and venous sinuses have no valves, therefore blood within them can flow in either direction.