Lateral C1–C2 dislocation complicating a type II odontoid fracture

We describe a unique C1–C2 lateral dislocation complicating a displaced type II odontoid fracture. We report a 63-year-old female pedestrian involved in a motor vehicle accident who required posterior open reduction and segmental C1–C2 instrumentation and fusion. Radiological examination of the cervical spine demonstrated a lateral dislocation of the atlantoaxial joint with a displaced type II fracture of the odontoid, fracture of the right lateral mass of C1 and left superior articular facet of C2. Neurological examination revealed the patient to be myelopathic and closed halo traction failed to achieve reduction. Due to the irreducible nature of the dislocation, posterior open reduction and segmental C1–C2 instrumentation and fusion was performed. The dislocated C1–C2 articulation was successfully reduced surgically with subsequent bony fusion and resolution of all neurological symptoms and signs at final follow-up. To our knowledge, this the first report of this type of injury. We also review the related literature on this unique injury pattern.     

5HT–2C receptor polymorphism in suicide victims

Abstract. Sustainable observations suggest that suicidal behaviour by itself may have biological correlates, among which those related to the serotonergic synapse hold the key position. Based on the association of suicide and serotonergic dysfunction, it was proposed that genetic mechanisms affecting suicidal behaviour could be related to the alterations of the genes encoding the elements of 5HT synapse. The present study tested the association of the polymorphism in the serotonin 2C (5HT-2C) receptor coding region (Cys23Ser) with suicide commitment. Study was based on two independent samples, one of German (284 suicide victims versus 297 controls) and other of Slavic/Croatian (118 suicide victims versus 275 controls) ethnicity. No significant differences in allele or genotype frequencies between victims and controls were demonstrated. Results did not provide supporting evidence for the potential involvement of the investigated variants of 5HT-2C receptor in the susceptibility to suicide.     

Retinal axonal degeneration in Niemann–Pick type C disease

Journal of Neurology - Niemann–Pick disease type C1 (NPC1) is a rare autosomal-recessive lysosomal storage disorder presenting with a broad clinical spectrum ranging from a severe...     

Altered 13C glucose metabolism in the cortico–striato–thalamo–cortical loop in the MK-801 rat model of schizophrenia

Using a modified MK-801 (dizocilpine) N-methyl--aspartic acid (NMDA) receptor hypofunction model for schizophrenia, we analyzed glycolysis, as well as glutamatergic, GABAergic, and monoaminergic neurotransmitter synthesis and degradation. Rats received an injection of MK-801 daily for 6 days and on day 6, they also received an injection of [1-¹³C]glucose. Extracts of frontal cortex (FCX), parietal and temporal cortex (PTCX), thalamus, striatum, nucleus accumbens (NAc), and hippocampus were analyzed using ¹³C nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, and gas chromatography–mass spectrometry. A pronounced reduction in glycolysis was found only in PTCX, in which ¹³C labeling of glucose, lactate, and alanine was decreased. ¹³C enrichment in lactate, however, was reduced in all areas investigated. The largest reductions in glutamate labeling were detected in FCX and PTCX, whereas in hippocampus, striatum, and Nac, ¹³C labeling of glutamate was only slightly but significantly reduced. The thalamus was the only region with unaffected glutamate labeling. γ-Aminobutyric acid (GABA) labeling was reduced in all areas, but most significantly in FCX. Glutamine and aspartate labeling was unchanged. Mitochondrial metabolites were also affected. Fumarate labeling was reduced in FCX and thalamus, whereas malate labeling was reduced in FCX, PTCX, striatum, and NAc. Dopamine turnover was decreased in FCX and thalamus, whereas that of serotonin was unchanged in all regions. In conclusion, neurotransmitter metabolism in the cortico–striato–thalamo–cortical loop is severely impaired in the MK-801 (dizocilpine) NMDA receptor hypofunction animal model for schizophrenia.     

Photomyogenic response in Niemann–Pick type C: a case report

Journal of Neurology -     

Niemann–Pick disease type C: introduction and main clinical features

Journal of Neurology -     

Treatment of Niemann–Pick Type C Disease by Histone Deacetylase Inhibitors

Niemann–Pick type C disease (NPC) is a devastating, recessive, inherited disorder that causes accumulation of cholesterol and other lipids in late endosomes and lysosomes. Mutations in 2 genes, NPC1 and NPC2, are responsible for the disease, which affects about 1 in 120,000 live births. About 95 % of patients have mutations in NPC1, a large polytopic membrane protein that is normally found in late endosomes. More than 200 missense mutations in NPC1 have been found in NPC patients. The disease is progressive, typically leading to death before the age of 20 years, although some affected individuals live well into adulthood. The disease affects peripheral organs, including the liver, spleen, and lungs, but the most severe symptoms are associated with neurological disease. There are some palliative treatments that slow progression of NPC disease. Recently, it was found that histone deacetylase (HDAC) inhibitors that are effective against HDACs 1, 2, and 3 can reduce the cholesterol accumulation in fibroblasts derived from NPC patients with mutations in NPC1. One example is vorinostat. As vorinostat is a Food and Drug Administration–approved drug for treatment of cutaneous T-cell lymphoma, this opens up the possibility that HDAC inhibitors could be repurposed for treatment of this rare disease. The mechanism of action of the HDAC inhibitors requires further study, but these drugs increase the level of the NPC1 protein. This may be due to post-translational stabilization of the NPC1 protein, allowing it to be transported out of the endoplasmic reticulum.     

C1 dome-like laminotomy and posterior C1–C2 polyaxial screw-rod fixation for a patient with cervical myelopathy due to a retro-odontoid pseudotumor

A 49-year-old man presented with progressive cervical myelopathy caused by a retro-odontoid mass, with associated developmental canal stenosis at C1, and C1–C2 instability. Surgery was scheduled for a dome-like laminotomy at C1, posterior C1–C2 fixation using C1 lateral mass screws and C2 pedicle screws, and structural bone grafting between C1 and C2. Prior to surgery, we produced a 3-dimensional full-scale model of the patient’s cervical spine and performed a simulation of the scheduled surgery. Through the simulation, we accurately evaluated the laminotomy sites and the screw insertion points. During the actual surgery, all procedures were successful. After surgery, the patient’s neurological deficits markedly improved. Successful C1–C2 fusion, adequate decompression of the spinal cord, and spontaneous regression of the retro-odontoid mass were achieved by this procedure without any apparent restriction in neck movement.     

Hepatitis C virus–related factors associated WITH cognitive performance in HIV-HCV-coinfected patients

Journal of NeuroVirology - The contribution of HCV-related variables to cognitive impairment in HIV-HCV-coinfected patients has been poorly investigated. We selected HIV-HCV-coinfected patients...     

L239F founder mutation in GDAP1 is associated with a mild Charcot–Marie–Tooth type 4C4 (CMT4C4) phenotype

Over 40 mutations in the GDAP1 gene have been shown to segregate with Charcot–Marie–Tooth disease (CMT). Among these, only two mutations, i.e., S194X and Q163X have been reported in a sufficient number of CMT families to allow for the construction of reliable phenotype–genotype correlations. Both the S194X and Q163X mutations have been shown to segregate with an early-onset and severe neuropathy resulting in loss of ambulance at the beginning of the second decade of life. In this study, we identified the L239F mutation in the GDAP1 gene in one Bulgarian and five Polish families. We hypothesized that the L239F mutation may result from a founder effect in the European population since this mutation has previously been reported in Belgian, Czech, and Polish patients. In fact, we detected a common disease-associated haplotype within the 8q13-q21 region in the Polish, German, Italian, Czech, and Bulgarian CMT families. Like the previously detected “regional” S194X and Q163X mutations, respectively present in Maghreb countries and in patients of Spanish descent, the L239F mutation seems to be the most common GDAP1 pathogenic variant in the Central and Eastern European population. Given the likely presence of a common ancestor harboring the L239F mutation, we decided to compare the phenotypes of the CMT (L239F) patients collected in this study with those of previously reported cases. In contrast to CMT4A caused by the S194X and Q163X mutations, the CMT phenotype resulting from the L239F substitution represents a milder clinical entity with a long-preserved period of ambulance at least until the end of the second decade of life.     

Niemann–Pick type C: focus on the adolescent/adult onset form

Niemann–Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment.     

Niemann–Pick disease type C1 presenting with psychosis in an adolescent male

Niemann–Pick disease, a neurovisceral lysosomal lipid storage disorder, is a rare disorder that is unknown to many clinicians. The disease, that often has its onset during childhood or adolescence, shows a polymorphic clinical picture, including psychiatric symptoms. Because of its infrequence, Niemann–Pick disease is diagnosed with an average delay of 6 years. This report presents a case of an adolescent male whose symptoms had led to various hospitalisations and psychiatric diagnoses. When he presented with psychotic symptoms in our department, thorough diagnosis revealed Niemann–Pick disease type C1 as the underlying disease.     

Lack of Niemann–Pick type C1 induces age-related degeneration in the mouse retina

Niemann–Pick type C (NPC) disease is an inherited lysosomal storage disease and caused by mutations in Npc1 or Npc2, which mediate cooperatively the egress of cholesterol from lysosomes. The disease entails progressive neurodegeneration, whose cause is poorly understood. Here, we report that Npc1 is distributed in distinct layers of the mouse retina and that its deficiency causes striking retinal degeneration in 2-month-old mice with signs of age-related maculopathies. This includes impaired visual function, accumulation of lipofuscin in the retinal pigment epithelium layer, degeneration of photoreceptor outer segments, disruption of synaptic layers and an increase in autophagy markers in the ganglion cell layer. Moreover, the lack of Npc1 results in the upregulation of proteins that mediate cellular cholesterol release in the retina. Our findings suggest that Npc1 is required for normal retinal function and that its absence may serve as model to study age-related degeneration of the retina.     

Neurological Dysfunction in Early Maturity of a Model for Niemann–Pick C1 Carrier Status

Autosomal recessive inheritance of NPC1 with loss-of-function mutations underlies Niemann–Pick disease, type C1 (NP-C1), a lysosomal storage disorder with progressive neurodegeneration. It is uncertain from limited biochemical studies and patient case reports whether NPC1 haploinsufficiency can cause a partial NP-C1 phenotype in carriers. In the present study, we examined this possibility in heterozygotes of a natural loss-of-function mutant Npc1 mouse model. We found partial motor dysfunction and increased anxiety-like behavior in Npc1 ^+/– mice by 9 weeks of age. Relative to Npc1 ^+/+ mice, Npc1 ^+/– mice failed to show neurodevelopmental improvements in motor coordination and balance on an accelerating Rotarod. In the open-field test, Npc1 ^+/– mice showed an intermediate phenotype in spontaneous locomotor activity compared with Npc1 ^+/+ and Npc1 ^–/– mice, as well as decreased center tendency. Together with increased stride length under anxiogenic conditions on the DigiGait treadmill, these findings are consistent with heightened anxiety. Our findings indicate that pathogenic NPC1 allele carriers, who represent about 0.66 % of humans, could be vulnerable to motor and anxiety disorders.     

Spasmodic torticollis: severe compression neuropathy in rami dorsales of cervical nerves C1–6

Summary In 28 patients with spasmodic torticollis dorsal branches of the cervical nerves C1–6, and in 25 of these patients fascicles of the contralateral accessory nerve were investigated by light and electron microscopy. Significant changes were noted in 15 patients. The alterations were not seen or were less prominent in the 5 control cases studied for comparison. Semiquantitative evaluation of light microscopic findings revealed in 12 cases prominent and numerous Renaut bodies; in 9 cases evidence of regeneration (in 3 of these postoperatively); and in 11 cases disproportionately thin myelin sheaths in relation to axon calibers. In conjunction with endoneurial edema and thickening of the perineurium, these changes were suggestive of compression neuropathy. Whether these changes were the cause, or a side effect of the abnormal muscle contractions in spasmodic torticollis could not be elucidated. Peripheral nerve compression, however, may trigger abnormal activity in the peripheral part of the involved interneuronal circuits and may, thus, be considered as one of the many possible causes of spasmodic torticollis.This study has been presented in part at the Arbeistagung Torticollis spasmodicus at Schloss Reisensburg, Günzburg, Federal Republic of Germany December 4th, 1990     

The phenotype of Charcot–Marie–Tooth disease type 4C due to SH3TC2 mutations and possible predisposition to an inflammatory neuropathy

Charcot–Marie–Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies. The locus responsible for CMT4C was previously assigned to the chromosome 5q23 region by homozygosity mapping and mutations in the SH3TC2 (KIAA1985) gene have been subsequently identified mainly in families around the Mediterranean basin but also frequently in European Gypsies. No English families have been reported to date. To determine the frequency, phenotype and neuropathology of CMT due to SH3TC2 mutations we screened 23 English autosomal recessive (AR) demyelinating CMT families. Five families with AR demyelinating CMT and SH3TC2 mutations were identified, four families were homozygous for the R954X mutation and the fifth family was compound heterozygous for the R954X and E657K mutations. There was significant clinical variation between these families with some cases presenting with a severe childhood onset neuropathy with respiratory and cranial nerve involvement, compared to other families with mild scoliosis and foot deformity. Characteristic sural nerve neuropathology was seen in three families with frequent demyelinating fibres surrounded by excess Schwann cell lamellae forming basal lamina onion bulbs and abnormally long and attenuated Schwann cell processes. One patient homozygous for the R954X mutation had a 20-year history of an inflammatory neuropathy that was superimposed onto the hereditary form, indicating that structural alterations to the SH3TC2 gene could possibly predispose to peripheral nerve inflammation.     

Bone–like Polyethelyne Burr–hole Cover

Abstract

Objective: Several materials are available for covering burr holes but none of them are ideal with respect to biocompatibility, strength and morbidity. With these properties in mind, our objective was to design a porous polyethylene device, which looked like bone and provides protection and cosmesis while being quick and easy to apply.

Methods and Materials/Results: A burr–hole cover was created to cover small cranial defects and craniostomies. Using high–density polyethylene, this cover was designed to resemble the bony structure of the skull. Its porous architecture allows for tissue ingrowth and bony integration. It consists of a cylinder which fits into the burr hole and a cap which can be sutured or anchored with titanium screws.

Conclusions: The 'bone–like' burr–hole cover provides adequate protection, biocompatibility and cosmesis and is simple to use. Alternative implants can be toxic to surrounding tissues, costly and time consuming to apply. This high–density polyethylene cover is compatible with surrounding tissue as well as being of a porous nature and the material it is made from offers high tensile strength for adequate protection.     

Opsoclonus–myoclonus–ataxia syndrome in children

Journal of Neurology - Opsoclonus–myoclonus–ataxia syndrome is a rare neuroimmunologic disorder typically presenting in previously healthy infants and toddlers. It is characterized by a...