A Pyramidal Cause of a Cerebellar Ataxia:HSP-7

A 43-year-old man presented with a slowly progressive fatigue and coordination problems, coupled with a radiological appearance of diffuse atrophy, especially in the cerebellar hemispheres. The diagnostic process was challenging because initially the additional investigations were focused on a cerebellar ataxia. In the following months, his ataxic gait developed in a more spastic pattern and whole exome sequencing revealed mutations in the SPG7 gene, confirming a diagnosis of hereditary spastic paraplegia. Therefore, the authors call for an extension of genetic panels in ataxia patients

Patients with mild traumatic brain injury and acute neck pain at the emergency department are a distinct category within the mTBI spectrum:a prospective multicentre cohort study

Background: Acute neck pain (ANP) has recently been demonstrated to be a predictor of persistent posttraumatic complaints after mild traumatic brain injury (mTBI). The aim of this study was to determine specific characteristics of patients with ANP following mTBI, their posttraumatic complaints and relationship with functional outcome. Methods: Data from a prospective follow-up study of 922 mTBI patients admitted to the emergency department (ED) in three level-one trauma centres were analysed. Patients were divided into two groups: 156 ANP patients and 766 no acute neck pain (nANP) patients. Posttraumatic complaints were evaluated 2 weeks and 6 months post-injury using standardized questionnaires and functional outcome was evaluated at 6 months with the Glasgow Outcome Scale Extended (GOSE). Results: ANP patients were more often female (p < 0.01), younger (38 vs. 47 years, p < 0.01) with more associated acute symptoms at the ED (p < 0.05) compared to nANP patients. More motor vehicle accidents (12% vs. 6%, p = 0.01) and less head wounds (58% vs. 73%, p < 0.01) in ANP patients indicated 'high-energy low-impact' trauma mechanisms. ANP patients showed more posttraumatic complaints 2 weeks and 6 months post-injury (p < 0.05) and more often incomplete recovery (GOSE < 8) was present after 6 months (56% vs. 40%, p = 0.01). Conclusions: MTBI patients with acute neck pain at the ED constitute a distinct group within the mTBI spectrum with specific injury and demographic characteristics. Early identification of this at risk group already at the ED might allow specific and timely treatment to avoid development of incomplete recovery

Mutations in Potassium Channel KCND3 Cause Spinocerebellar Ataxia Type 19

OBJECTIVE: To identify the causative gene for the neurodegenerative disorder spinocerebellar ataxia type 19 (SCA19) located on chromosomal region 1p21-q21. METHODS: Exome sequencing was used to identify the causal mutation in a large SCA19 family. We then screened 230 ataxia families for mutations located in the same gene (KCND3, also known as Kv4.3) using high-resolution melting. SCA19 brain autopsy material was evaluated, and in vitro experiments using ectopic expression of wild-type and mutant Kv4.3 were used to study protein localization, stability, and channel activity by patch-clamping. RESULTS: We detected a T352P mutation in the third extracellular loop of the voltage-gated potassium channel KCND3 that cosegregated with the disease phenotype in our original family. We identified 2 more novel missense mutations in the channel pore (M373I) and the S6 transmembrane domain (S390N) in 2 other ataxia families. T352P cerebellar autopsy material showed severe Purkinje cell degeneration, with abnormal intracellular accumulation and reduced protein levels of Kv4.3 in their soma. Ectopic expression of all mutant proteins in HeLa cells revealed retention in the endoplasmic reticulum and enhanced protein instability, in contrast to wild-type Kv4.3 that was localized on the plasma membrane. The regulatory β subunit Kv channel interacting protein 2 was able to rescue the membrane localization and the stability of 2 of the 3 mutant Kv4.3 complexes. However, this either did not restore the channel function of the membrane-located mutant Kv4.3 complexes or restored it only partially. INTERPRETATION: KCND3 mutations cause SCA19 by impaired protein maturation and/or reduced channel function

Supplementary Material for: A Pyramidal Cause of a Cerebellar Ataxia: HSP-7

A 43-year-old man presented with a slowly progressive fatigue and coordination problems, coupled with a radiological appearance of diffuse atrophy, especially in the cerebellar hemispheres. The diagnostic process was challenging because initially the additional investigations were focused on a cerebellar ataxia. In the following months, his ataxic gait developed in a more spastic pattern and whole exome sequencing revealed mutations in the SPG7 gene, confirming a diagnosis of hereditary spastic paraplegia. Therefore, the authors call for an extension of genetic panels in ataxia patients

Pitfalls in clinical assessment of neurotoxic diseases: negative effects of repeated diagnostic evaluation, illustrated by a clinical case

Exposure to different toxic substances can have acute and chronic neurological and neuropsychiatric health effects on humans. Patients often report impaired concentration and memory, irritability, fatigue, instability of affect and difficulties in impulse control. The diagnostic process for neurotoxic diseases is complex and relies heavily on the exclusion of differential diagnosis and substantiating the cognitive complaints by neuropsychological assessment. Diagnostic evaluations have the purpose to help the patient by finding an explanation for the symptoms to guide treatment strategy or prevent further deterioration. But what if the diagnostic process in itself leads to problems that can be quite persistent and difficult to manage? The iatrogenic, or sick-making, side effects of the diagnostic process are the main focus of this case stud

Herziene richtlijn 'Opvang van patiënten met licht traumatisch hoofd-hersenletsel'

Recently the out-of-date Dutch guideline 'Mild traumatic head/brain injury' dating from 2001 was revised under the supervision of the Dutch Institute for Healthcare Improvement (CBO). The revised guideline gives underpinned decision rules for the referral of patients to hospital, carrying out diagnostic imaging investigations, and formulating indications for admission. Mild head-brain injury is no longer an indication for a conventional skull radiograph. Adults and children aged 6 years and older no longer have to be woken regularly if they are allowed home. The guideline can be used in both primary care and on the Emergency Departments of hospitals and is applicable to both adults and children. The guideline does not address the rehabilitation or long-term care of patients with mild traumatic head/brain injury, but it does give advice on reducing the risk of long-term symptoms. Regional implementation of the guideline in primary and secondary care is recommende

Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure to solvents. One hundred and forty-five subjects referred to one of two Dutch national assessment centers for CTE were administered the Amsterdam Short-Term Memory Test (ASTM) and the Test of Memory Malingering (TOMM), two tests specifically developed for the detection of suboptimal performance. For both tests, very cautious cut-off scores were chosen with a specificity of 99%. Results indicated that suboptimal performance appears to be a substantial problem in this group of patients with suspected CTE after long-term. exposure to organic solvents. Only 54% of our subjects obtained normal scores oil both tests of malingering, i.e. at or above cut-off score. The two tests seemed to measure the same concept in that nearly all the subjects with low TOMM scores also had low ASTM scores. However a higher proportion of subjects scored below the cut-off on the ASTM than on the TOMM. (C) 2003 Elsevier Science Inc. All rights reserve