Nitrous Oxide-induced Myeloneuropathy Due to Recreational Abuse.

BACKGROUND: The recreational use of nitrous oxide (N2O) has increased in recent years with a noticeable surge in the incidence of nitrous oxide-related myeloneuropathy. OBJECTIVES: To raise awareness of increasing myeloneuropathy due to recreational nitrous oxide misuse in Israel. METHODS: We conducted a case series documenting the clinical and investigative features of eight patients presenting with nitrous oxide-induced myeloneuropathy who were admitted to our departments. RESULTS: Paresthesia was the chief complaint in all patients, with sensory gait ataxia being a common feature, which was often accompanied by Romberg's sign and mild lower limb weakness. Vitamin B12 levels were below the normal range in seven patients, accompanied by elevated homocysteine and methylmalonic acid levels. Magnetic resonance imaging scans revealed hyperintense signals in the dorsal columns of the cervical spine. All patients improved following vitamin B12 injections. CONCLUSIONS: Enhancing awareness, prompting the use of appropriate investigations, and advocating for timely treatment are needed to overcome the risks associated with nitrous oxide misuse.

Roussy-Lévy Syndrome: Pes Cavus, Tendon Areflexia, Amyotrophy, Gait Ataxia, and Upper Limb Tremor in a Patient with CMT Neuropathy.

Background: Roussy-Lévy syndrome (RLS) is characterized by postural hand tremor seen in patients with familial autosomal dominant Charcot-Marie-Tooth (CMT) neuropathy. Phenomenology Shown: This video demonstrates irregular, jerky bilateral kinetic, postural, rest tremor affecting the right > left hand, along with pes cavus and gait ataxia in a patient with CMT disease. Educational Value: Pes cavus, tendon areflexia, sensory ataxia, and upper limb tremor should prompt consideration of CMT neuropathy. Highlights: This video abstract depicts a bilateral hand tremor characteristic of Roussy-Lévy syndrome seen in patients with Charcot-Marie-Tooth disease neuropathy. The significance of the abstract lies in the phenomenology and the physiology of the tremor seen in patients with genetically confirmed duplication of PMP22 gene.

Different Purkinje cell pathologies cause specific patterns of progressive gait ataxia in mice.

Gait ataxia is one of the most common and impactful consequences of cerebellar dysfunction. Purkinje cells, the sole output neurons of the cerebellar cortex, are often involved in the underlying pathology, but their specific functions during locomotor control in health and disease remain obfuscated. We aimed to describe the effect of gradual adult-onset Purkinje cell degeneration on gaiting patterns in mice, and to determine whether two different mechanisms that both lead to Purkinje cell degeneration cause different patterns in the development of gait ataxia. Using the ErasmusLadder together with a newly developed limb detection algorithm and machine learning-based classification, we subjected mice to a challenging locomotor task with detailed analysis of single limb parameters, intralimb coordination and whole-body movement. We tested two Purkinje cell-specific mouse models, one involving stochastic cell death due to impaired DNA repair mechanisms (Pcp2-Ercc1-/-), the other carrying the mutation that causes spinocerebellar ataxia type 1 (Pcp2-ATXN1[82Q]). Both mouse models showed progressive gaiting deficits, but the sequence with which gaiting parameters deteriorated was different between mouse lines. Our longitudinal approach revealed that gradual loss of Purkinje cell function can lead to a complex pattern of loss of function over time, and that this pattern depends on the specifics of the pathological mechanisms involved. We hypothesize that this variability will also be present in disease progression in patients, and that our findings will facilitate the study of therapeutic interventions in mice, as subtle changes in locomotor abilities can be quantified by our methods.

Gait disorders induced by photothrombotic cerebellar stroke in mice.

Patients with cerebellar stroke display relatively mild ataxic gaits. These motor deficits often improve dramatically; however, the neural mechanisms of this improvement have yet to be elucidated. Previous studies in mouse models of gait ataxia, such as ho15J mice and cbln1-null mice, have shown that they have a dysfunction of parallel fiber-Purkinje cell synapses in the cerebellum. However, the effects of cerebellar stroke on the locomotor kinematics of wild-type mice are currently unknown. Here, we performed a kinematic analysis of gait ataxia caused by a photothrombotic stroke in the medial, vermal, and intermediate regions of the cerebellum of wild-type mice. We used the data and observations from this analysis to develop a model that will allow locomotive prognosis and indicate potential treatment regimens following a cerebellar stroke. Our analysis showed that mice performed poorly in a ladder rung test after a stroke. During walking on a treadmill, the mice with induced cerebellar stroke had an increased duty ratio of the hindlimb caused by shortened duration of the swing phase. Overall, our findings suggest that photothrombotic cerebellar infarction and kinematic gait analyses will provide a useful model for quantification of different types of acute management of cerebellar stroke in rodents.

Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia.

Familial dysautonomia (FD) is a rare neurodegenerative disease caused by a splicing mutation in elongator acetyltransferase complex subunit 1 (ELP1). This mutation leads to the skipping of exon 20 and a tissue-specific reduction of ELP1, mainly in the central and peripheral nervous systems. FD is a complex neurological disorder accompanied by severe gait ataxia and retinal degeneration. There is currently no effective treatment to restore ELP1 production in individuals with FD, and the disease is ultimately fatal. After identifying kinetin as a small molecule able to correct the ELP1 splicing defect, we worked on its optimization to generate novel splicing modulator compounds (SMCs) that can be used in individuals with FD. Here, we optimize the potency, efficacy, and bio-distribution of second-generation kinetin derivatives to develop an oral treatment for FD that can efficiently pass the blood-brain barrier and correct the ELP1 splicing defect in the nervous system. We demonstrate that the novel compound PTC258 efficiently restores correct ELP1 splicing in mouse tissues, including brain, and most importantly, prevents the progressive neuronal degeneration that is characteristic of FD. Postnatal oral administration of PTC258 to the phenotypic mouse model TgFD9;Elp1Δ20/flox increases full-length ELP1 transcript in a dose-dependent manner and leads to a 2-fold increase in functional ELP1 in the brain. Remarkably, PTC258 treatment improves survival, gait ataxia, and retinal degeneration in the phenotypic FD mice. Our findings highlight the great therapeutic potential of this novel class of small molecules as an oral treatment for FD.

¿Un síntoma negado? Lateropulsión parietal de la marcha como manifestación inicial de ictus isquémico agudo / A neglected symptom? Parietal gait lateropulsion as primary manifestation of acute is-chemic stroke

Introducción: Los trastornos de la marcha no suelen considerarse dentro de las manifestaciones de presentación del ictus y están subrepresentados en las series de casos. Presentamos cuatro casos de lateropulsión de la marcha de inicio súbito como manifestación primaria de ictus del lóbulo parietal.Caso clínico: Cuatro pacientes se presentaron tras el inicio súbito de lateropulsión de la marcha. En el examen neurológico, todos tenían al menos un déficit sensitivo cortical, marcha de base amplia con lateropulsión ipsilateral al déficit cortical. En la neuroimagen se corroboró un ictus subagudo parietal contralateral al lado de lateropulsión de la marcha. Dos pacientes tenían lateropulsión bilateral con predominio ipsilateral al déficit cortical e incremento de inestabilidad con los ojos cerrados (simulando signo de Romberg), en quienes la neuroimagen demostró un ictus parietal bilateral (subagudo contralateral, crónico ipsilateral al lado de lateropulsión de la marcha). Conclusión: Describimos la lateropulsión de la marcha como una nueva manifestación inicial de ictus agudo del lóbulo parietal (lateropulsión parietal de la marcha), contralateral al lado de desviación de la marcha. Dado el papel del parietal como destino de las vías de propiocepción, los ictus pueden originar alteraciones de la marcha, con lesiones bilaterales que semejan ataxia sensitiva con inestabilidad al eliminar la aferencia visual.(AU)

Introduction: Gait disorders are commonly overlooked as a presenting manifestation of stroke and underrepresented in case series. We describe four cases of sudden-onset gait lateropulsion as primary manifestation of parietal lobe stroke. Case report: Four patients presented after sudden-onset gait lateropulsion. On neurological examination, all patients had at least one cortical sensory deficit and wide-based gait with lateropulsion towards the side of the cortical deficit. Neuroimaging revealed a subacute parietal lobe stroke contralateral to the side of gait lateropulsion. In two patients we found bilateral lateropulsion with predominance towards the side of cortical deficit and increase of unsteadiness with eye closure (an apparent Romberg sign), with neuroimaging revealing bilateral parietal strokes (subacute contralateral and chronic ipsilateral to gait lateropulsion).Conclusion: We report gait lateropulsion as a novel primary manifestation of acute stroke of the parietal lobe (parietal gait lateropulsion). Given its role as the destination of proprioceptive pathways, parietal strokes can result in gait lateropulsion, with bilateral lesions even mimicking sensory ataxia with bilateral lateropulsion and unsteadiness upon eye closure.(AU)

Consensus Paper: Ataxic Gait.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.

Postoperative Acute-Phase Gait Training Using Hybrid Assistive Limb Improves Gait Ataxia in a Patient with Intradural Spinal Cord Compression Due to Spinal Tumors.

Sensory ataxia due to posterior cord syndrome is a relevant, disabling condition in nontraumatic spinal cord dysfunction. Ataxic gait is a common symptom of sensory ataxia that restricts activities of daily living. A 70-year-old woman with severe sensory disturbance was diagnosed with intradural extramedullary spinal cord tumors found in the thoracic spine region (T8). Surgical management of the tumors was performed. The patient received gait training 20 days after surgery (postoperative acute phase) using a hybrid assistive limb (HAL). HAL is a wearable exoskeleton cyborg that provides real-time assistance to an individual for walking and limb movements through actuators mounted on the bilateral hip and knee joints. Walking ability was assessed using the 10 m walking test, which included evaluating walking speed, step length, and cadence in every session. To evaluate the immediate effects of HAL training, walking speed and step length were measured before and after the training in each session. During the 10 m walking test, gait kinematics and lower muscle activity were recorded using a motion capture system and wireless surface electromyography before the first session and after completion of all HAL sessions. After the HAL training sessions, improvement in the patient's gait performance was observed in the gait joint angles and muscle activity of the lower limb. After 10 training sessions, we observed the following changes from baseline: walking speed (from 0.16 m/s to 0.3 m/s), step length (from 0.19 m to 0.37 m), and cadence (from 50.9 steps/min to 49.1 steps/min). The average standard deviations of the knee (from right, 7.31; left, 6.75; to right, 2.93; p < 0.01, left, 2.63; p < 0.01) and ankle joints (from right, 6.98; left, 5.40; to right, 2.39; p < 0.01, left, 2.18; p < 0.01) were significantly decreased. Additionally, walking speed and step length improved immediately after completing all the HAL training sessions. This suggests that HAL gait training might be a suitable physical rehabilitation program for patients with sensory ataxia causing dysfunctional movement of the lower limb.

Craniovertebral Junction Anomalies: An Overlooked Cause of 'Posterior Circulation Stroke'.

Background: Vertebral artery dissection (VAD) is a treatable cause of vertebrobasilar ischemic stroke and can be spontaneous or more commonly traumatic. Craniovertebral junction (CVJ) anomalies are a rare and often overlooked cause of VAD. Objective: The objective of this study was to study cases where CVJ anomaly presented as posterior circulation infarct and to conduct a relevant literature review. Materials and Methods: The medical records of seven patients who were managed for posterior circulation infarct associated with CVJ anomaly at our center from January 2009 through August 2013 were reviewed. PubMed and MEDLINE databases were also searched for similar cases, and the published case reports/series were reviewed. Results: Seven patients met our inclusion criteria and were included in the study. The mean age was 17.4 years (range: 10-35 years). All the patients were males. The most common symptoms were headache, vomiting, and gait ataxia. Slurring of speech was seen in one patient. One patient had repeated episodes of gait ataxia with left-sided weakness with complete recovery in between the episodes. One patient presented in unconscious state. Four patients complained of vertigo. The median duration of symptoms was 7 days (range: 3 days-12 months). Conclusions: CVJ anomalies can present as posterior circulation infarct. One must evaluate all patients with posterior circulation stroke, especially young patients, for possible CVJ anomalies. Dynamic lateral cervical spine X-ray is an important tool to diagnose AAD. CVJ anomalies represent a treatable cause of VAD.

mVEGAS - mobile smartphone-based spatiotemporal gait analysis in healthy and ataxic gait disorders.

BACKGROUND: Quantitative gait assessment is increasingly applied in fall risk stratification, diagnosis, and disease monitoring of neuro-geriatric gait disorders. Its broad application, however, demands for low-cost and mobile solutions that facilitate high-quality assessment outside laboratory settings. The aim of this study was to present and evaluate the concurrent validity of a mobile and low-cost gait assessment tool (mVEGAS) that combines body-fixed inertial sensors and a smartphone-based video capture for spatiotemporal identification of gait sequences. METHODS: Initially, we examined potential interferences of wearing mVEGAS with walking performance in a cohort of 20 young healthy individuals (31.1 ± 10.1 years; 8 females). Subsequently, we assessed the concurrent validity of mVEGAS as compared to a pressure-sensitive gait carpet (GAITRite) in a cohort of 26 healthy individuals (55.8 ± 14.3 years; 10 females) and 26 patients (55.7 ± 14.0; 14 females) with moderate to severe degrees of cerebellar gait ataxia. All participants were instructed to walk at preferred, slow, and fast walking speed and standard average and variability gait measures including velocity, stride length, stride time, base of support, swing and double support phase were examined for agreement between the two systems by absolute error and intraclass correlation coefficients (ICC). RESULTS: Wearing mVEGAS did only marginally interfere with normal walking behavior. mVEGAS-derived average and variability gait measures exhibited good to excellent concurrent validity in healthy individuals (ICCs ranging between 0.645 and 1.000) and patients with gait ataxia (ICCs ranging between 0.788 and 1.000) SIGNIFICANCE: mVEGAS may facilitate high-quality and long-term gait monitoring in different non-specialized environments such as medical practices, nursing homes or community centers.

Power and connectivity changes on electroencephalogram in postoperative cerebellar mutism.

INTRODUCTION: Cerebellar mutism syndrome is a debilitating postoperative neurological complication following posterior fossa surgery in children. It is characterized by a significant lack or loss of speech. Injury to the dentato-thalamo-cortical pathway is thought to be the main anatomical substrate of cerebellar mutism syndrome; however, few studies have investigated the physiological changes using computed electroencephalogram. CASE REPORT: Herein, we report a case of a nine-year-old girl who developed cerebellar mutism syndrome after excision of an ependymoma of the fourth ventricle and was followed up with evaluation of aphasia, gross motor function, and scalp electroencephalograms. Her language, dysmetria and gait ataxia gradually improved until day 605 after onset. Computed electroencephalogram analyses were performed for the relative power spectrum and connectivity at each frequency band. On the three electroencephalograms at days 109, 299, and 605 after onset, the relative power spectrum at the delta band transiently decreased and then increased, and the relative power spectrums at theta, beta, and gamma bands transiently increased and then decreased. Only the relative power spectrum in the alpha band continuously increased in the occipital area. Additionally, brain connectivity in the delta, beta, and gamma bands increased continuously. CONCLUSION: We report a case of cerebellar mutism syndrome with recovery of language, dysmetria and gait ataxia in 20 months. Electroencephalogram analyses indicated transient changes in the powers of brain activity and continuous improvements in connectivity during the long follow-up, reflecting the plasticity and remodeling of brain function after cerebellar mutism syndrome. Power and connectivity analyses for EEG might be a tool to investigate underlying pathophysiology of cerebellar mutism syndrome.

Longitudinally extensive dorsal column spinal cord lesion with sensory ganglionopathy.

We present a case of a 23-year-old woman with a history of celiac disease who presented with a 2-month history of progressive gait unsteadiness and falls. Neurologic examination exhibited preserved motor strength, diffuse areflexia, and ataxic gait. Autoimmune and infectious workups were unremarkable, including vitamin B12. Electrodiagnostic testing showed absent diffuse sensory responses, consistent with sensory ganglionopathy. Total spine magnetic resonance imaging (MRI) revealed a non-enhancing, posterior cord, hyperintense signal from C1-T11. Partial improvement in her sensory ataxia was noted after 6 months of high-dose steroids without dorsal cord signals change on repeat MRI that suggests Wallerian degeneration of sensory axons.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (canvas): an important cause of late-onset ataxia with unique clinical features.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slowly progressive disorder characterized by cerebellar ataxia, sensory neuropathy and bilateral vestibulopathy. Recently, a biallelic intronic AAGGG repeat expansion, (AAGGG)exp, in the Replication Factor C1 (RFC1) gene was identified as the cause of this disorder. In this study, we describe the phenotypic features of five patients from five different families diagnosed as CANVAS. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. Our study describes clinical findings, histopathological features and diagnostic clues of CANVAS from Turkey, a country with a high consanguineous marriage rate. Repeat expansion in the RFC1 gene should be considered in all cases with late-onset ataxia, especially when sensory disturbances, vestibular involvement and persistent coughing coexist.

Case Report: Homozygous DNAJC3 Mutation Causes Monogenic Diabetes Mellitus Associated With Pancreatic Atrophy.

Introduction: DNAJC3, abundant in the pancreatic cells, attenuates endoplasmic reticulum stress. Homozygous DNAJC3 mutations have been reported to cause non-immune juvenile-onset diabetes, neurodegeneration, hearing loss, short stature, and hypothyroidism. Case Description: We report a case of homozygous DNAJC3 mutation in two siblings of a consanguineous family. A 3-year-old boy presented with short stature and a thyroid nodule. Laboratory findings confirmed hypothyroidism. Subsequently, levothyroxine was administered. Growth hormone (GH) stimulation test results were within the normal limits. His stature was exceedingly short (80.5 cm) (-3.79 SDS). The patient developed sensorineural hearing loss at age 6 years; his intellectual functioning was impaired. Recombinant Human Growth Hormine (rhGH) treatment was postponed until the age of 6.9 years due to a strong family history of diabetes. At age 9 years, he developed an ataxic gait. Brain magnetic resonance imaging (MRI) revealed neurodegeneration. The patient developed diabetes at the age of 11 years-5 years after the initiation of rhGH treatment. Tests for markers of autoimmune diabetes were negative. Lifestyle modification was introduced, but insulin therapy was eventually required. Whole-exome-sequencing (WES) revealed a homozygous DNAJC3 mutation, which explained his clinical presentation. MRI revealed a small, atrophic pancreas. At the age of 17, his final adult height was 143 cm (-4.7 SDS). His elder brother, who had the same mutation, had a similar history, except that he had milder ataxia and normal brain MRI finding at the age of 28 years. Conclusion: We propose that DNAJC3 mutation can be considered as a cause of maturity onset diabetes of the young. Patients with DNAJC3 mutations may possess a small atrophic pancreas.

Cerebellar Long Noncoding RNA Expression Profile in a Niemann-Pick C Disease Mouse Model.

Niemann-Pick type C (NP-C) disease is a neurodegenerative lysosomal storage disorder primarily caused by mutations in NPC1. However, its pathogenesis remains poorly understood. While mounting evidence has demonstrated the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of neurodegenerative disorders, the lncRNA expression profile in NP-C has not been determined. Here, we used RNA-seq analysis to determine lncRNA and mRNA expression profiles of the cerebella of NPC1-/- mice. We found that 272 lncRNAs and 856 mRNAs were significantly dysregulated in NPC1-/- mice relative to controls (≥ 2.0-fold, p < 0.05). Quantitative real-time PCR (qRT-PCR) was utilized to validate the expression of selected lncRNAs and mRNAs. Next, a lncRNA-mRNA coexpression network was employed to examine the potential roles of the differentially expressed (DE) lncRNAs. Functional analysis revealed that mRNAs coexpressed with lncRNAs are mainly linked to immune system-related processes and neuroinflammation. Moreover, knockdown of the lncRNA H19 ameliorated changes in ROS levels and cell viability and suppressed the lipopolysaccharide (LPS)-induced inflammatory response in vitro. Our findings indicate that dysregulated lncRNA expression patterns are associated with NP-C pathogenesis and offer insight into the development of novel therapeutics based on lncRNAs.

Complement Component C3 Loss leads to Locomotor Deficits and Altered Cerebellar Internal Granule Cell In Vitro Synaptic Protein Expression in C57BL/6 Mice.

Complement component 3 (C3) expression is increased in the cerebellum of aging mice that demonstrate locomotor impairments and increased excitatory synapse density. However, C3 regulation of locomotion, as well as C3 roles in excitatory synapse function, remains poorly understood. Here, we demonstrate that constitutive loss of C3 function in mice evokes a locomotor phenotype characterized by decreased speed, increased active state locomotor probability, and gait ataxia. C3 loss does not alter metabolism or body mass composition. No evidence of significant muscle weakness or degenerative arthritis was found in C3 knockout mice to explain decreased gait speeds. In an enriched primary cerebellar granule cell culture model, loss of C3 protein results in increased excitatory synaptic density and increased response to KCl depolarization. Our analysis of excitatory synaptic density in the cerebellar internal granule cell and molecular layers did not demonstrate increased synaptic density in vivo, suggesting the presence of compensatory mechanisms regulating synaptic development. Functional deficits in C3 knockout mice are therefore more likely to result from altered synaptic function and/or connectivity than gross synaptic deficits. Our data demonstrate a novel role for complement proteins in cerebellar regulation of locomotor output and control.

Hypocupraemia-induced anaemia, sensory ataxia and cognitive impairment secondary to zinc-containing dental adhesive.

A 67-year-old man presented with 5 months of worsening memory impairment and sensory gait ataxia on the background of symptomatic anaemia. He experienced falls, agitation and became socially withdrawn over 3 weeks, resulting in hospital admission. On examination, he had sensory gait ataxia consistent with a dorsal column syndrome. He scored 13/30 on the Montreal Cognitive Assessment. Serum analysis showed normocytic anaemia and leucopenia, severe hypocupraemia, reduced caeruloplasmin and normal zinc levels. Overuse of zinc-containing denture cream was the cause of excess zinc ingestion and resultant copper deficiency, leading to blood dyscrasia and myelopathy. The cream was withdrawn and intravenous and then oral copper supplementation was implemented. Direct questions with regard to excess zinc in the diet and serological testing of copper and zinc should be considered in any patient with a dorsal column syndrome, particularly with concurrent anaemia. Copper deficiency may also have a role in exacerbating pre-existing cognitive impairment.

Neurological Evaluation of Patients with Newly Diagnosed Coeliac Disease Presenting to Gastroenterologists: A 7-Year Follow-Up Study.

We have previously shown that 67% of patients with newly diagnosed coeliac disease (CD) presenting to gastroenterologists have evidence of neurological dysfunction. This manifested with headache and loss of co-ordination. Furthermore 60% of these patients had abnormal brain imaging. In this follow-up study, we re-examined and re-scanned 30 patients from the original cohort of 100, seven years later. There was significant reduction in the prevalence of headaches (47% to 20%) but an increase in the prevalence of incoordination (27% to 47%). Although those patients with coordination problems at baseline reported improvement on the gluten free diet (GFD), there were 7 patients reporting incoordination not present at baseline. All 7 patients had positive serology for one or more gluten-sensitivity related antibodies at follow-up. In total, 50% of the whole follow-up cohort were positive for one or more gluten-related antibodies. A comparison between the baseline and follow-up brain imaging showed a greater rate of cerebellar grey matter atrophy in the antibody positive group compared to the antibody negative group. Patients with CD who do not adhere to a strict GFD and are serological positive are at risk of developing ataxia, and have a significantly higher rate of cerebellar atrophy when compared to patients with negative serology. This highlights the importance of regular review and close monitoring.

Complications following equine sacroiliac region analgesia are uncommon: A study in 118 horses.

BACKGROUND: Diagnosis of sacroiliac region pain is supported by a positive response to sacroiliac region analgesia (SIRA). Varying techniques have been described for SIRA; with clinician preference often dictating method. Potential complications following SIRA include ataxia and recumbency. No study has specifically evaluated the prevalence of complications. OBJECTIVES: To describe the complication prevalence following SIRA in a referral clinic. STUDY DESIGN: Retrospective cohort study. METHODS: Review of records from horses presented to two of the authors at Rossdales, Newmarket, between January 2014 and December 2018, that underwent SIRA. Injection was performed using a blind midline approach with 20 mL mepivacaine (Intra-Epicaine 20mg/ml; Dechra) infiltrated through a straight 18 gauge 8.9cm spinal needle subdivided into four sub-locations per block. RESULTS: 118 horses were included, with 167 individual blocks. One horse showed a mild hindlimb gait abnormality following SIRA, which resolved uneventfully over 3 hours; complication rate 1/118 horses (0.85%; 95% CI: 0,2.5%), 1/167 joints (0.60%; 95% CI: 0,1.8%). SIRA subjectively improved lameness/performance in 132/167 (79%) joints. 49/118 (42%) received bilateral SIRA with 53/118 (45%) evaluated ridden following SIRA. MAIN LIMITATIONS: Small population numbers with low complication prevalence rate. CONCLUSIONS: SIRA, using the described technique, has a low (0.85%) prevalence of complications.