Hoskote Chandrashekar

An ITPR1 gene deletion causes spinocerebellar ataxia 15/16: a genetic, clinical and radiological description.

the purpose of this study was to characterise a novel family with very slowly progressive pure spinocerebellar ataxia (SCA) caused by a deletion in the inositol 1,4,5‐triphosphate receptor 1 (ITPR1) gene on chromosome 3. This is a detailed clinical, genetic, and radiological description of the genotype. Deletions in ITPR1 have been shown to cause SCA15/SCA16 in six families to date. A further Japanese family has been identified with an ITPR1 point mutation. The exact prevalence is as yet unknown, but is probably higher than previously thought. The clinical phenotype of the family is described, and videotaped clinical examinations are presented. Serial brain magnetic resonance imaging studies were carried out on one affected individual, and genetic analysis was performed on several family members. Protein analysis confirmed the ITPR1 deletion. Affected subjects display a remarkably slow, almost pure cerebellar syndrome. Serial magnetic resonance imaging shows moderate cerebellar atrophy with mild inferior parietal and temporal cortical volume loss. Genetic analysis shows a deletion of 346,487 bp in ITPR1 (the second largest ITPR1 deletion reported to date), suggesting SCA15 is due to a loss of ITPR1 function. Western blotting of lymphoblastoid cell line protein confirms reduced ITPR1 protein levels. SCA15 is a slowly or nonprogressive pure cerebellar ataxia, which appears to be caused by a loss of ITPR1 function and a reduction in the translated protein. Patients with nonprogressive or slowly progressive ataxia should be screened for ITPR1 defects.

Movement Disorders in Adult Patients With Classical Galactosemia

Classical galactosemia is an autosomal recessive inborn error of metabolism leading to toxic accumulation of galactose and derived metabolites. It presents with acute systemic complications in the newborn. Galactose restriction resolves these symptoms, but long‐term complications, such as premature ovarian failure and neurological problems including motor dysfunction, may occur despite adequate treatment. The objective of the current study was to determine the frequency and phenotype of motor problems in adult patients with classical galactosemia. In this cross‐sectional study, adult patients with a biochemically confirmed diagnosis of galactosemia attending our clinic were assessed with an interview and neurological examination and their notes retrospectively reviewed. Patients were classified according to the presence/absence of motor dysfunction on examination. Patients with motor dysfunction were further categorized according to the presence/absence of reported motor symptoms. Forty‐seven patients were included. Thirty‐one patients showed evidence of motor dysfunction including: tremor (23 patients), dystonia (23 patients), cerebellar signs (6 patients), and pyramidal signs (4 patients). Tremor and dystonia were often combined (16 patients). Thirteen patients reported motor symptoms, with 8 describing progressive worsening. Symptomatic treatment was effective in 4 of 5 patients. Nonmotor neurological features (cognitive, psychiatric, and speech disorders) and premature ovarian failure were more frequent in patients with motor dysfunction. Motor dysfunction is a common complication of classical galactosemia, with tremor and dystonia the most frequent findings. Up to one third of patients report motor symptoms and may benefit from appropriate treatment. Progressive worsening is not uncommon and may suggest ongoing brain damage in a subset of patients.

Atypical parkinsonism and cerebrotendinous xanthomatosis: Report of a family with corticobasal syndrome and a literature review

Cerebrotendinous xanthomatosis is an autosomal recessive inborn error of cholesterol metabolism. It presents with systemic and neurological symptoms, rarely including parkinsonism. Presented here are a clinical description of a new family with cerebrotendinous xanthomatosis and parkinsonism and a review of 13 additional cases reported in the literature. The index case developed corticobasal syndrome, previously not reported in cerebrotendinous xanthomatosis. His brother had parkinsonism with cerebellar features and cognitive impairment. In a literature review, median age of onset of parkinsonism was found to be 40 years. Nearly all patients had other neurological symptoms: cognitive (93%), pyramidal (93%), or cerebellar (53%). All patients had walking difficulties, with falls in 27%. Systemic features were common: cataracts (93%) or tendon xanthomata (87%). Frequent MRI abnormalities included cerebellar atrophy (100%), cerebral atrophy (80%), and dentate nuclei signal changes (80%). Functional dopaminergic imaging often demonstrated presynaptic denervation. Improvement with levodopa was frequent (91%) but mild. Progressive neurological decline occurred in 92% of patients despite treatment with chenodeoxycholic acid. Cerebrotendinous xanthomatosis should be considered in the differential diagnosis of atypical parkinsonism, including corticobasal syndrome, particularly with early age of onset and in the context of a complex neurological phenotype. Tendon xanthomata, early‐onset cataracts, and radiological findings of cerebellar atrophy with lesions of the dentate nuclei are useful clinical clues. Symptomatic treatment with levodopa may help, but progressive neurological decline is frequent despite treatment with chenodeoxycholic acid.

Stability of ruptured intracranial aneurysms treated with detachable coils: is delayed follow-up angiography warranted?

The optimal strategy for monitoring the stability of ruptured intracranial aneurysms following coil embolisation is unclear. The value of delayed follow-up angiography in detecting new recurrences or progression of residual lesions visualised on earlier angiographic studies was determined in the light of the increasing use of non-invasive imaging techniques such as time of flight magnetic resonance angiography (TOF-MRA) for the evaluation of intracranial aneurysm occlusion. Ninety-seven patients with 105 ruptured aneurysms treated with detachable coils in 2005 and 2006 were included. The presence of a residual neck or aneurysm was assessed on catheter angiograms performed at 6 months and 2 years using the Raymond criteria (Class I = completely occluded, class II = small residual neck, class III = aneurysm sac filling). At 6-month follow-up, 32% of class I aneurysms progressed to class II and 6% of these aneurysms required re-treatment. A further 2-year angiogram was obtained in 59 patients with 65 aneurysms. Ninety-six per cent of class I, 100% of the class II and class III aneurysms remained unchanged at 2 years compared to 6 months. In our series, most recurrences were apparent at 6-month follow-up. The vast majority of coiled ruptured aneurysms that were class I or II at 6 months remained stable at 2-year follow-up. In the absence of a residual lesion in the early angiographic study, a further delayed catheter angiogram may not be warranted. The use of non-invasive strategies such as TOF-MRA should be considered.

Angiography and selective microcatheter embolization of a falcine meningioma supplied by the artery of Davidoff and Schechter. Case report.

Angiographic demonstration of the meningeal branch of the posterior cerebral artery, or the artery of Davidoff and Schechter, is extremely rare. The authors describe a case of successful selective catheterization and embolization of a pathologically enlarged artery of Davidoff and Schechter, permitting successful preoperative devascularization of a large falcine meningioma.

An automated multiscale ensemble simulation approach for vascular blood flow

This work has received funding from the CRESTA project within the EC-FP7 (ICT-2011.9.13) under Grant Agreements no. 287703, and from EPSRC Grants EP/I017909/1 (www.2020science.net) and EP/I034602/1.

Imaging of parasitic infections of the central nervous system.

Parasitic infections of the central nervous system (CNS) have increased over the last couple of decades, partly due to a drop in the living conditions of large populations in the world and the AIDS epidemic. Parasitic infections of the CNS are indolent and often life threatening, hence, an early diagnosis is imperative. While brain biopsy and laboratory analysis remain the gold standard for diagnosis, neuroimaging contributes significantly to diagnosis and follow-up. Imaging can demonstrate the extent of infection and complications and possibly, the type of parasitic infection when characteristic features are evident. The disappearance of the parasite or inflammation, gliosis, and/or calcification suggest a therapeutic response. The initial experience of the CT scan has been greatly enhanced by MRI which is currently the imaging modality of choice. This has been due to the greater tissue contrast resolution of MRI and its ability to detect subtle changes in the tissue parenchyma. Advanced techniques such as diffusion-weighted imaging (DWI), perfusion imaging (PI), MR angiography (MRA), and MR spectroscopy (MRS) have been used to improve the sensitivity for characterizing the type, viability, and burden of the parasites and the host tissue response. Additionally, it is possible to demonstrate the complications of the primary infection and those secondary to treatment, in some cases.

Cranial nerve, spinal root and plexus hypertrophy in chronic inflammatory demyelinating polyneuropathy

A middle-aged patient with a history of chronic inflammatory demyelinating polyneuropathy of over 20 years presented with new onset of numbness of the penis and impaired erections. Review of the clinical history revealed an initial presentation in his early 20s with an unsteady gait and numbness of the feet, following which he developed progressive asymmetric distal weakness and sensory loss of his lower and upper limbs. Previous electrophysiological studies had demonstrated a demyelinating sensorimotor polyneuropathy with absent sensory nerve action potentials and markedly decreased motor nerve conduction velocities (8 m/s in the right median nerve). Raised protein content (3 g/l) had been established on cerebrospinal fluid analysis and sural nerve biopsy revealed ‘onion bulb’ formation …

Chronic immune sensory polyradiculopathy with cranial and peripheral nerve involvement

Chronic immune sensory polyradiculopathy (CISP) is a recently described restricted form of chronic inflammatory demyelinating polyradiculopathy (CIDP) [1]. It preferentially affects large myelinated fibres of the posterior roots, is associated with normal peripheral nerve conduction studies, and may respond to immunomodulatory treatment. We describe a patient with clinical features of CISP and additional cranial nerve involvement. A 61 year old woman presented with a 10 year relapsing-remitting neurological disorder. She initially presented with nausea, headache and photophobia followed by diplopia and unilateral ptosis consistent with an oculomotor nerve palsy. Intracranial CT, MRI, MRA, catheter angiography and CSF were all normal. Symptoms resolved over 18 months but an inflammatory cause was suspected after a relapse and treatment with 2 g/kg intravenous immunoglobulin (IVIg) was effective. Further relapses with additional poor balance, facial numbness and distal sensory symptoms responded promptly to IVIg. Intravenous methylprednisolone worsened her symptoms. Neurological examination revealed a partial right oculomotor nerve palsy. Pin prick sensation was reduced in a right trigeminal nerve distribution. Limb power was normal but reflexes were reduced in the upper limbs and absent in the lower limbs with flexor plantars. Romberg’s test was positive. Pin prick was reduced on the ulnar aspect of the right forearm and up to the mid-shins bilaterally. Vibration sense was reduced up to both ankles and proprioception impaired up to the right ankle. Examination after IVIg revealed that ophthalmoplegia, ptosis and a timed Romberg’s test had all improved. Systemic inflammatory/autoimmune blood tests were unremarkable and these included full blood count, ESR, CRP, ANA, ANCA, complement, rheumatoid factor, ENA, protein electrophoresis, immunofixation, acetylcholine receptor antibodies, immunoglobulins, ganglioside serology, lyme serology, treponemal serology and anti-neuronal antibodies. CSF was acellular with normal glucose and a raised protein level of 0.71 g/L (normal 0.15–0.65 g/L). Oligoclonal bands were absent. Neurophysiological data are presented in the appendix. In summary, the absolute values of all neurophysiological investigations listed were normal. However, the ulnar nerve SNAPs were significantly asymmetrical and the motor F-waves prolonged. Thermal thresholds were abnormal in the feet and right hand. Somatosensory evoked potentials were poorly formed in the right lower limb. Asymmetry of motor evoked potential latencies following cervical spine stimulation was consistent with a lesion distal to the intervertebral foramina. Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-6326-0) contains supplementary material, which is available to authorized users.

Auditory rehabilitation after stroke: treatment of auditory processing disorders in stroke patients with personal frequency-modulated (FM) systems.

Abstract Purpose: Auditory disability due to impaired auditory processing (AP) despite normal pure-tone thresholds is common after stroke, and it leads to isolation, reduced quality of life and physical decline. There are currently no proven remedial interventions for AP deficits in stroke patients. This is the first study to investigate the benefits of personal frequency-modulated (FM) systems in stroke patients with disordered AP. Methods: Fifty stroke patients had baseline audiological assessments, AP tests and completed the (modified) Amsterdam Inventory for Auditory Disability and Hearing Handicap Inventory for Elderly questionnaires. Nine out of these 50 patients were diagnosed with disordered AP based on severe deficits in understanding speech in background noise but with normal pure-tone thresholds. These nine patients underwent spatial speech-in-noise testing in a sound-attenuating chamber (the “crescent of sound”) with and without FM systems. Results: The signal-to-noise ratio (SNR) for 50% correct speech recognition performance was measured with speech presented from 0° azimuth and competing babble from ±90° azimuth. Spatial release from masking (SRM) was defined as the difference between SNRs measured with co-located speech and babble and SNRs measured with spatially separated speech and babble. The SRM significantly improved when babble was spatially separated from target speech, while the patients had the FM systems in their ears compared to without the FM systems. Conclusions: Personal FM systems may substantially improve speech-in-noise deficits in stroke patients who are not eligible for conventional hearing aids. FMs are feasible in stroke patients and show promise to address impaired AP after stroke. Implications for Rehabilitation This is the first study to investigate the benefits of personal frequency-modulated (FM) systems in stroke patients with disordered AP. All cases significantly improved speech perception in noise with the FM systems, when noise was spatially separated from the speech signal by 90° compared with unaided listening. Personal FM systems are feasible in stroke patients, and may be of benefit in just under 20% of this population, who are not eligible for conventional hearing aids.