Supracondylar femur fracture complicating epileptic insult: a specific and under diagnosed complication?

PURPOSE: In epileptic patients fractures are six times more frequent than in the general population. Known predisposing factors are anticonvulsant drugs, malnutrition, lack of physical activity and sunlight exposure. METHODS: In this study we describe two patients, one with a bilateral supracondylar fracture and one with a unilateral supracondylar fracture after an epileptic seizure. The literature concerning femur fracture following an epileptic insult is reviewed. RESULTS: A review of the literature revealed several cases of femur fractures associated with epilepsy, however no cases were found involving a supracondylar femur. CONCLUSIONS: Our hypothesis is that a tonic seizure with simultaneous contraction of both agonists and antagonists can cause this type of fracture in predisposing patients.     

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

Journal of Neurology -     

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.     

Rigid variety occiput/C1–C2–C3 internal fixation in pediatric population

Purpose

The purpose of this study was to review our experience of rigid internal fixation of craniovertebral junction in pediatric population. A new technique of reduction of basilar invagination with atlantoaxial dislocation is described. To the best of our knowledge and available scientific literature, this technique has not yet been described in younger patients.

Methods

We have managed 27 children by rigid variety of occiput/C1–C2–C3 internal fixation of various craniovertebral junction pathologies. All patients were subjected to thin cuts of computed tomography with 3D reconstruction for selecting appropriate rigid construct. Eight children had occiput-C2, 3 had occiput-C2–C3, and 16 had C1-C2 hardware constuct. One patient of C1–C2-plate fixation had section of C2 nerve root ganglia. Basilar invagination with atlantoaxial dislocation was reduced by new distraction/compression techniques.

Results

Improvement in clinical features and correction of deformity with solid hardware construct were seen in all patients. Follow-up period ranged from 5–72 months. One patient was lost to follow-up, and one case died of compression of vertebral artery at C1 lateral mass. Patients of myelopathy had recovery rate of 90.9 %. Hardware failure was seen in one patient, and wound infection was observed in two cases.

Conclusions

Rigid variety of occiput/C1–C2 internal fixation is a safe and effective method in the management of variety of craniovertebral pathologies in pediatric population. This new technique of reduction of basilar invagination with atlantoaxilal dislocation from posterior approach may alleviate the need of high morbity associated with surgical procedure like transoral odontoidectomy in younger patients.     

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.     

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.     

Evolution of Charcot–Marie–Tooth disease type 1A duplication: a 2-year clinico-electrophysiological and lower-limb muscle MRI longitudinal study

The objective of this study was to analyze Charcot–Marie–Tooth disease type 1A (CMT1A) evolution. We conducted a 2-year longitudinal study in 14 CMT1A patients and 14 age- and sex-matched controls. In the patients, we performed neurological examination with hand-held dynamometry, electrophysiology, and lower-limb muscle MRI, both at baseline and 2 years later, while controls were examined at baseline only. Patients’ ages ranged from 12 to 51 years. Outstanding manifestations on initial evaluation included pes cavus, areflexia, lower-limb weakness, and foot hypopallesthesia. In evaluating muscle power, good correlation was observed between manual testing and dynamometry. Compared to controls, Lunge, 10-Meter-Walking, and 9-Hole-Peg tests were impaired. Their CMT neuropathy score and functional disability scale showed that patients exhibited mild phenotype and at most slight walking difficulty. Electrophysiology revealed marked nerve conduction slowing and variable compound muscle action potential amplitude reduction. On lower-limb muscle MRI, there was distally accentuated fatty infiltration accompanied by edema in calf muscles. All these clinico-electrophysiological and imaging findings remained almost unaltered during monitoring. Using multivariate analysis, no significant predictors of progression associated to the disease were obtained. We conclude that in the 2-year period of study, CMT1A patients showed mild progression with good concordance between clinico-electrophysiological and imaging findings.     

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.     

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...     

Clinical spectrum and gender differences in a large cohort of Charcot–Marie–Tooth type 1A patients

IntroductionHeterogeneous clinical presentation and gender differences were reported in Charcot–Marie–Tooth disease type 1A (CMT1A).MethodsThis report examined demographic and clinical data collected during a randomised controlled trial, to describe the clinical spectrum of a large and well-defined cohort of CMT1A patients.ResultsAmong the 189 symptomatic patients screened, three patients (1.6%) reported first symptoms in the upper limbs, which may be misleading when establishing the clinical diagnosis. The quality of life (QoL) of patients was significantly deteriorated compared to the standard population, and slightly better compared to multiple sclerosis patients. According to the literature, patients reported several disorders which may be associated with CMT1A, including auditory dysfunction (7.9%), Carpal Tunnel Syndrome (CTS) (7.9%) or sleep apnoea (4.2%). Compared to available data, we reported more patients with CTS and fewer patients with sleep apnoea. Women were more affected by CTS than men (11% and 2.8%, respectively). Women also reported an earlier onset of symptoms than men (8.6 ± 9.5 years and 13.1 ± 14 years, respectively), higher deterioration of their QoL and higher disability of their upper limb, assessed by Overall Neuropathy Limitation Scale (p = 0.023).ConclusionsThis information will be useful for better understanding of this disease and for designing future clinical studies.     

A novel AIFM1 mutation in a Chinese family with X-linked Charcot–Marie–Tooth disease type 4

X-linked Charcot–Marie–Tooth disease type 4 (CMTX4), caused by AIFM1 (Apoptosis-Inducing Factor, Mitochondrion associated 1) mutations and associated with deafness and cognitive impairment, is a rare subtype of Charcot–Marie–Tooth disease. Here, we report a novel missense variant of AIFM1 in a X-linked recessive Chinese family with childhood-onset, slowly progressive, isolated axonal motor and sensory neuropathy. Calf magnetic resonance imaging revealed fatty infiltration and atrophy severely involving the muscles of peroneal compartment. Pathologies exhibited abnormal mitochondrial morphology and accumulation in axoplasm of nerve fiber and subsarcolemmal area of muscle. A hemizygous variant (c.513G>A, p.Met171Ile) in the family was identified and was classified as likely pathogenic according to the standards and guidelines of the American College of Medical Genetics and Genomics. Our report expands the genetic spectrum of diseases related to AIFM1 mutations and indicates that fatty infiltration and atrophy of muscles in the peroneal compartment may be a feature of CMTX4 in early stage.     

Adenine nucleotide translocase is involved in a mitochondrial coupling defect in MFN2-related Charcot–Marie–Tooth type 2A disease

Charcot–Marie–Tooth type 2A disease (CMT2A), a dominantly inherited peripheral neuropathy, is caused by mutations in MFN2, a mitochondrial fusion protein. Having previously demonstrated a mitochondrial coupling defect in CMT2A patients’ fibroblasts, we here investigate mitochondrial oxygen consumption and the expression of adenine nucleotide translocase (ANT) and uncoupling proteins from eight other patients with the disease. The mitochondrial uncoupling was associated with a higher respiratory rate, essentially involving complex II proteins. Furthermore, a twofold increase in the expression of ANT led to the reduced efficiency of oxidative phosphorylation in CMT2A cells, suggesting that MFN2 plays a role in controlling ATP/ADP exchanges.     

Time-trend evolution and determinants of sex ratio in Amyotrophic Lateral Sclerosis: a dose–response meta-analysis

Journal of Neurology - A noticeable change of the male-to-female sex ratio (SR) has been observed in Amyotrophic Lateral Sclerosis (ALS) leading to an apparent regression of SR with time (SR close...     

Retrospective study on PET–SPECT imaging in a large cohort of myotonic dystrophy type 1 patients

The aim was to study brain involvement in myotonic dystrophy type 1 by single photon emission tomography (SPECT) and positron emission tomography (PET). 58 DM1 patients were subjected to SPECT; 17 to both SPECT and PET. SPECT patients were grouped as ‘normally perfused’ and ‘abnormally perfused’; PET patients as ‘normal performers’ and ‘abnormal performers’. To quantify hypoperfusion and/or hypometabolism, we used a semi-quantitative scale. To localize focal hypoperfusion/hypometabolism, nine cerebral areas of involvement were identified. The Chi-square, Wilcoxon, McNemar tests were used for statistics. SPECT showed abnormalities in 52/58 patients. PET showed an abnormal glucidic uptake in 15/17. Hypoperfusion was mild/moderate in 50/58 patients, mostly involving the left supratentorial areas. Abnormal glucidic uptake was mainly observed in the left frontal lobe. Abnormalities in blood perfusion and/or glucose metabolism are frequent in DM1. These abnormalities involve the left more often than the right hemisphere, the frontal lobe more than other lobes. Such abnormalities are more often cortical than subcortical.     

Clinical and radiological Comparison of treatment of atlantoaxial instability by posterior C1–C2 transarticular screw fixation or C1 lateral mass-C2 pedicle screw fixation

We compared the clinical and radiological results of posterior atlantoaxial fixation surgery using transarticular screws to those using a polyaxial screw–rod system in 55 patients with symptomatic atlantoaxial instability. Patients underwent posterior C1–C2 fixation: 28 patients (group 1) underwent C1–C2 transarticular screw fixation and 27 patients (group 2) underwent C1 lateral mass–C2 pedicle screw fixation. Patients were followed-up for at least 24 months. The clinical and radiological results were evaluated in the early postoperative period and at 3, 6, 12 and 24 months after surgery. Long-term postoperative stability and bone fusion were examined. After surgery, 93% of patients in group 1 and 96% of patients in group 2 were free of neck pain. The solid fusion rates were 82% for group 1 patients and 96% for group 2 patients at 12 months (p < 0.092). In group 1, three patients showed fibrous union. Four patients had hardware failure due to a screw malposition (one in group 1) and pseudoarthrodesis (two in group 1 and one in group 2). One patient in group 1 had cerebrospinal fluid leakage. One patient in group 2 had occipital neuralgia. One vertebral artery injury occurred during the screw placement in group 1 and another in group 2 during the muscle dissection. C1–C2 transarticular screw fixation and C1 lateral mass–C2 pedicle screw fixation both produced excellent results for stabilization of the atlantoaxial complex, but the radiological outcome tended to be superior in C1 lateral mass–C2 pedicle screw fixation.