X-linked cerebral adrenoleukodystrophy.

A man in his 30s presented with a 6-month history of progressive left face, arm and leg weakness. Medical history included epilepsy and vitamin B12 deficiency. Three maternal second degree relatives died before the age of 7 from various neurological disorders. Examination revealed a mild left facial droop and weakness of the left shoulder, hip and ankle. Reflexes were symmetrical and tone was normal. Differential diagnosis included glioma, subacute infarction, lymphoma and demyelination. MRI brain showed an extensive right sided subcortical white matter lesion, with extension into the brainstem. The patient's weakness progressed over 3 months. Brain biopsy showed evidence of demyelination and gliosis. A pathological diagnosis of tumefactive multiple sclerosis was made, but also rare metabolic disorders such as X-linked adrenoleukodystrophy (X-ALD) were proposed. Serum very long-chain fatty acids were significantly elevated. Genetic testing showed a mutation in the ABCD1 gene, confirming a diagnosis of X-ALD.

Case report: Dueling etiologies: Longitudinally extensive spinal cord lesion mimicking spinal cord infarct with simultaneous positive Lyme serology and amphiphysin antibody.

Background: Longitudinally extensive spinal cord lesions are challenging diagnostic entities as they are uncommon, but various etiologies can cause them. Case report: We report a case of a 55-year-old man with a past medical history of hypertension. He is an ex-smoker. He presented with chest pain, followed by right lower limb weakness, preceded by 2 weeks of constipation and voiding dysfunction. The examination revealed right lower limb mild flaccid paresis, absent reflexes, reduced anal tone, and urinary retention. His symptoms deteriorated over 24 h, and he developed severe flaccid paraparesis with impaired pinprick sensation below the T4 level. MRI spine showed an abnormal, non-enhancing signal in the anterior aspect of the spinal cord extending from the T4 level to the conus without associated edema. He was commenced on intravenous steroids and had significant improvement after one dose. The imaging was felt to be consistent with spinal cord infarction, and aspirin was started. The cerebrospinal fluid analysis showed elevated protein (0.8 mg/ml). Investigations for stroke and autoimmune pathologies were negative. The Lyme immunoblot confirmed intrathecal production of IgG to Borrelia antigens. The patient was started on ceftriaxone. The paraneoplastic screen identified amphiphysin antibodies. CT-TAP and PET-CT did not identify occult malignancy. The patient had a significant improvement over 2 months, strength was almost fully recovered, and autonomic functions returned to normal. Conclusion: We describe an unusual steroid-responsive, longitudinally extensive spinal cord lesion with radiological features of spinal cord infarct and a simultaneous finding of intrathecal Lyme antibodies and serum amphiphysin antibodies.

Outcomes of implementation of the FilmArray meningoencephalitis panel in a tertiary hospital between 2017 and 2020.

BACKGROUND: Acute meningoencephalitis is encountered commonly in the acute hospital setting and is associated with significant morbidity and mortality, in addition to significant healthcare costs. Multiplex PCR panels now allow syndromic testing for central nervous system infection. The BioFire® FilmArray® Meningoencephalitis (ME) allows testing of 14 target pathogens using only 0.2mls of cerebrospinal fluid (CSF). We conducted a retrospective observational study to assess the performance of the assay and secondarily to observe the clinical utility of negative results by comparing clinical outcomes of aseptic meningitis to bacterial and viral meningoencephalitis. METHODS: Data for CSF samples tested using the FilmArray ME panel from October 2017 to October 2020 were analysed. Detection of bacterial and viral targets was analysed. Admission to critical care area, 90-day readmission rates, average length of stay and 30-day and 90-day mortality were analysed for three groups with following diagnoses: bacterial meningitis, viral meningoencephalitis, or aseptic meningitis. RESULTS: From October 2017 to October 2020, 1926 CSF samples were received in the Clinical Microbiology laboratory. Of those, 543 CSF samples from 512 individual patients were tested using the FilmArray ME panel. Twenty-one bacterial targets and 56 viral targets were detected during the study period. For viral targets, the cumulative specificity was 98.9% (95% confidence interval: 93.1-99.9) when compared to the reference laboratory methods. The outcomes for 30- and 90-day mortality of the aseptic meningitis group were non-inferior relative to the viral meningoencephalitis and bacterial meningitis group. Patients with bacterial meningitis had a longer average length of stay. Aseptic meningitis was associated with a higher 90-day readmission rate than the other 2 groups, but without statistical significance. CONCLUSION: In our hands, implementation of the FilmArray ME panel was relatively straightforward. We experienced a transition in our workflow processes that enabled streamlining of CSF diagnostics and the safe removal of Gram staining in those samples being tested by this molecular assay. Coupled to this improvement, there was a positive clinical impact on patient care due to rapid turnaround time to results.

Late-onset ornithine transcarbamylase deficiency mimicking a focal opercular syndrome.

A previously healthy 27-year-old man was brought to hospital after been found late at night confused, agitated and talking incoherently. He represented 12 days later with focal seizures, progressing to anarthria and encephalopathy. MR scan of brain showed diffuse cerebral oedema and his plasma ammonia was >2000 µmol/L (12-55 µmol/L). He developed refractory status epilepticus and subsequently died. Genetic analysis identified an ornithine transcarbamylase (OTC) gene mutation on the X chromosome. We discuss this atypical presentation of OTC deficiency as a rare but treatable cause of hyperammonaemic encephalopathy.

Paraneoplastic neurologic syndromes with multiple neural autoantibodies: A report of two cases.

We present two patients who presented with classical paraneoplastic syndromes with multiple central nervous system (CNS) autoantibodies in each case. The presence of multiple antibodies made the detection of a malignancy more likely and both patients were subsequently diagnosed with small cell lung carcinoma (SCLC). We highlight that the presence of multiple CNS autoantibodies increases the likelihood of detecting a malignancy but that the clinical presentation and response to treatment can vary despite similar antibody profiles. Clinicians should be alert to the need to search for occult malignancy in patients with multiple CNS autoantibodies.

Moyamoya disease and moyamoya syndrome in Ireland: patient demographics, mode of presentation and outcomes of EC-IC bypass surgery.

BACKGROUND: There are no previously published reports regarding the epidemiology and characteristics of moyamoya disease or syndrome in Ireland. AIMS: To examine patient demographics, mode of presentation and the outcomes of extracranial-intracranial bypass surgery in the treatment of moyamoya disease and syndrome in Ireland. METHODS: All patients with moyamoya disease and syndrome referred to the National Neurosurgical Centre during January 2012-January 2019 were identified through a prospective database. Demographics, clinical presentation, radiological findings, surgical procedures, postoperative complications and any strokes during follow-up were recorded. RESULTS: Twenty-one patients were identified. Sixteen underwent surgery. Median age at diagnosis was 19 years. Fifteen were female. Mode of presentation was ischaemic stroke in nine, haemodynamic TIAs in eight, haemorrhage in three and incidental in one. Sixteen patients had Moyamoya disease, whereas five patients had moyamoya syndrome. Surgery was performed on 19 hemispheres in 16 patients. The surgical procedures consisted of ten direct (STA-MCA) bypasses, five indirect bypasses and four multiple burr holes. Postoperative complications included ischaemic stroke in one patient and subdural haematoma in one patient. The median follow-up period in the surgical group was 52 months; there was one new stroke during this period. Two patients required further revascularisation following recurrent TIAs. One patient died during follow-up secondary to tumour progression associated with neurofibromatosis type 1. CONCLUSIONS: Moyamoya is rare but occurs in Caucasians in Ireland. It most commonly presents with ischaemic symptoms. Surgical intervention in the form of direct and indirect bypass is an effective treatment in the majority of cases.

Ciprofloxacin-associated choreoathetosis in a haemodialysis patient.

This report describes a case of drug-associated choreoathetosis in a patient receiving ciprofloxacin. A 72-year-old haemodialysis patient presented with a 4-day history of progressive weakness, restlessness and involuntary movements of all limbs. He had been prescribed ciprofloxacin 500 mg twice daily for a lower respiratory tract infection 7 days previously. He had generalised choreoathetosis affecting both upper and lower limbs. The temporal relationship with drug exposure and a dose which was on the upper limit for his renal impairment implicated ciprofloxacin as the culprit. His symptoms completely resolved within 1 week of drug withdrawal and never recurred subsequently.

Parkinsonism can be cured.

This case describes a woman with a history of rheumatoid arthritis with secondary vasculitic skin ulcers, Sicca syndrome and idiopathic Parkinson's disease that was diagnosed by a neurologist in 2005. The patient's parkinsonian symptoms were difficult to control, despite the use of antiparkinsonian medications. During a regular clinical review in 2011, the patient's rheumatologist had prescribed cyclophosphamide infusions to help with the vasculitic skin ulcers. Over the following 2 months, the patient's parkinsonian symptoms completely resolved.

Dilatation induced by 5-HT in the middle meningeal artery of the anaesthetised cat.

In chloralose-anaesthetised cats, we studied the effects of intravenous and intra-carotid injections of 5-HT on the middle meningeal artery and the way these were modified by 5-HT antagonists. Cats were prepared for blood pressure recording and intravenous injections and a catheter inserted into one carotid artery via a lingual artery. The middle meningeal arteries were exposed and blood flow recorded with laser Doppler probes. Intravenous injections of 5-HT, 2-50 microg kg(-1) (5.2-129 nmole kg(-1)), produced a dose-dependent fall in blood pressure, a rise in meningeal blood flow, and an associated fall in middle meningeal resistance. Resistance changes were the result of a local dilatation and not due to changes downstream of the recording probe. Intracarotid injections of 5-HT produced similar systemic and craniovascular responses, which were larger in the ipsilateral middle meningeal artery. Dose-response curves of vascular resistance changes to intravenous injection of 5-HT were not significantly affected by WAY100635 (5-HT1A antagonist), GR127935 (5-HT(1B/1D) antagonist), methiothepin (5-HT2C and 5-HT7 antagonist), ketanserin (5-HT2A antagonist), SB203186 (5-HT4 antagonist) or cervical sympathectomy, but were blocked by the 5-HT(3/4) antagonist tropisetron, the 5-HT3 antagonist ondansetron, the ganglion-blocking drug hexamethonium and by vagotomy. These drugs and procedures did not significantly antagonise the response to intra-arterially injected 5-HT. We conclude that intravenously-administered 5-HT is a vasodilator in vivo in the cat dural circulation, and that the dilation is not mediated by 5-HT1, 5-HT2, 5-HT4 or 5-HT7 receptors, but is primarily mediated by a vagal reflex, initiated via 5-HT3 receptor activation and brought about by an increase in parasympathetic tone to the middle meningeal artery as part of the von Bezold-Jarisch reflex. There also appears to be a direct vasodilator effect mediated by unknown receptor types, particularly after intra-arterial administration. Neither of these effects is, however, likely to be of importance in the pathophysiology of migraine or other vascular headaches.

The role of 5-HT1B and 5-HT1D receptors in the selective inhibitory effect of naratriptan on trigeminovascular neurons.

The importance of 5-HT(1B) and 5-HT(1D) receptors in the actions of the anti-migraine drug naratriptan was investigated using the relatively selective 5-HT(1) receptor ligands SB224289 and BRL15572. Electrical stimulation of the superior sagittal sinus (SSS) in cats activated neurones in the trigeminal nucleus caudalis. Facial receptive fields (RF) were also electrically stimulated to activate the same neurones. Responses of these neurones to SSS stimulation were suppressed by iontophoretic application of naratriptan (5-50 nA). There were two distinct populations of neurones in the nucleus--those in deeper laminae in which the responses to SSS and RF stimulation were equally suppressed by naratriptan ('non-selective') and more superficial neurones in which only the SSS responses were suppressed by naratriptan ('selective'). Concurrent micro-iontophoretic application (50 nA) of the 5-HT(1D) antagonist BRL15572 antagonised the suppression by naratriptan of the response of 'selective' cells to SSS stimulation. Iontophoretic application of SB224289 (50 nA), a 5-HT(1B) antagonist, antagonised the suppression by naratriptan of responses of 'non-selective' cells to RF stimulation and, to a lesser extent, also antagonised the suppression of responses to SSS stimulation. Intravenous administration of SB224289 antagonised the suppression only of RF responses of "non-selective" neurons by naratriptan and intravenous administration of BRL15572 antagonised the suppression only of SSS responses of "selective" neurons by naratriptan. These results suggest that the response of nucleus caudalis neurons to stimulation of the sagittal sinus can be modulated by both 5-HT(1B) and 5-HT(1D) receptor activation, with the 5-HT(1D) receptors perhaps playing a greater role. The response to RF stimulation is more influenced by 5-HT(1B) receptor modulation with 5-HT(1D) receptors being less important. Therefore, this suggests that selective 5-HT(1D) agonists may be able to target the neuronal population, which is selectively involved in the transmission of dural inputs. We conclude that the central terminals of trigeminal primary afferent fibres contain 5-HT(1B) and 5-HT(1D) receptors. Primary afferents from the dura mater may predominantly express 5-HT(1D) receptors, while facial afferents may predominantly express 5-HT(1B) receptors. Activation of 5-HT(1D) receptors in particular may be important in the anti-migraine effect of naratriptan.