Recurrent generalized seizures, visual loss, and palinopsia as phenotypic features of neuronal ceroid lipofuscinosis due to progranulin gene mutation.

We detail the phenotype of a novel form of neuronal ceroid lipofuscinosis due to a homozygous progranulin gene mutation (c.813_816del; CLN11 MIM #614706). The symptoms appeared in two young adult siblings, and included progressive retinopathy, recurrent generalized seizures, moderate ataxia, and subtle cognitive dysfunction. Long-lasting episodes of palinopsia were a recurring symptom and associated with polyphasic visual-evoked potential waveform that suggested hyperexcitability of the occipital cortex. Electroencephalography showed rare spike-wave paroxysms, and magnetic resonance imaging revealed selective cerebellar atrophy. Skin biopsy revealed fingerprint storage and the absence of progranulin protein. Electron microscopy of peripheral blood leukocytes showed fingerprint profiles in 1/100 lymphocytes. These findings define a novel phenotype and provide clues for better understanding of progranulin function. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Tethered cord: natural history, surgical outcome and risk for Chiari malformation 1 (CM1): a review of 110 detethering.

The surgical results of this series of occult spina bifida seem better than the natural history registered in the long pre-operative period in terms of neurological deterioration. The major contribution to this result is attributed to neurophysiological monitoring that lowers the risks of permanent damage and increases the percentage of effective detethering. The present series of TCS, due to conus and filar lipoma, documents that CM1 is a really rare association occurring in less than 6% of the patients, despite the low position of conus. The detethering procedure did not influence the tonsillar position, thus excluding the correlation between the tethering and the tonsillar descent. The genetic alteration documented in a girl reinforces the hypothesis of a rare complex polymaformative picture deserving multiple procedures according to the prevailing clinical symptoms.

Systemic sagopilone (ZK-EPO) treatment of patients with recurrent malignant gliomas.

It has been demonstrated that sagopilone (ZK-EPO) has antitumor activity in human orthotopic glioma models in vitro and in vivo. The objective of this study was to evaluate the safety and efficacy of ZK-EPO in patients with pretreated, recurrent malignant gliomas. Fifteen patients with recurrent malignant gliomas who had received prior surgery, radiotherapy, and >or=2 lines of alkylating chemotherapy were recruited. ZK-EPO (16 mg/m(2)) was administered iv for 3 h every 21 days. The primary end point was six months progression-free survival (PFS-6); secondary end points were safety, toxicity, response rate, and median time to progression (TTP). Magnetic resonance imaging (MRI) evaluations were performed every two cycles and toxicity was evaluated at each cycle using common terminology criteria for adverse events (CTCAE 3.0). A median of four cycles was administered. The median TTP was 13 weeks. PFS-6 was achieved in five patients (33%), three with glioblastoma multiforme and two with anaplastic astrocytoma. The most common treatment-related adverse event was neuropathy, which occurred in 6/15 patients. ZK-EPO had an acceptable safety profile and clinically relevant activity in patients with pretreated, recurrent malignant gliomas.

Two cases of thymoma-associated myasthenia gravis without antibodies to the acetylcholine receptor.

Thymoma-associated myasthenia gravis is considered a more severe disease compared with non-thymomatous myasthenia gravis and is generally associated with antibodies to the acetylcholine receptor (AChR-Ab). Even though a single case of thymoma-associated myasthenia gravis with anti-muscle specific kinase (MuSK) antibodies has been reported, to our knowledge, seronegative thymoma-associated myasthenia gravis has not been described. We report on two cases of this disease without antibodies to AChR or MuSK as a further evidence of the variability of myasthenia gravis in terms of antibody profile and thymic pathological findings.

Peripheral neuropathy due to paclitaxel: study of the temporal relationships between the therapeutic schedule and the clinical quantitative score (QST) and comparison with neurophysiological findings.

Peripheral neuropathy (PN) is one of the most common and dose-limiting side effects of paclitaxel, a chemiotherapeutic drug of proven efficacy in various tumours. We investigated the pathophysiological features of the PN and the temporal relationships between the development of the symptoms and signs associated with paclitaxel administration in two groups of patients with breast cancer: group A received paclitaxel alone (total cumulative dose range: 950-2,475 mg/m2), and group B paclitaxel and adriamycin (total cumulative dose range: 700-2,800 mg/m2). A codified assessment scoring clinical sensory and motor functions according to the Common Toxicity Scale and neurophysiological measurements were made before treatment, after the third and sixth cycles, and at the end of therapy. A total neuropathy score (TNS) included selected clinical and neurophysiological parameters. Both positive and negative sensory and motor symptoms and signs of PN developed during therapy, the most common being painful paresthesias, global areflexia and distal weakness. The neurophysiological study showed an early onset, length-independent and progressive sensory defect, and delayed, distal and length-dependent motor deficits. The neuropathy progressed faster in group A than in group B but, after therapy, most of the patients were TNS grade 2 regardless of their group. The temporal relationships between the PN and paclitaxel were robustly characterised, and thus provide reference data and a model for testing the efficacy of drugs designed to provide neuroprotection.

Rapid progression of late onset axonal Charcot-Marie-Tooth disease associated with a novel MPZ mutation in the extracellular domain.

Myelin protein zero (MPZ) is a major component of compact myelin in peripheral nerves where it plays an essential role in myelin formation and adhesion. MPZ gene mutations are usually responsible for demyelinating neuropathies, namely Charcot-Marie-Tooth (CMT) type 1B, Déjèrine-Sottas neuropathy and congenital hypomyelinating neuropathy. Less frequently, axonal CMT (CMT2) associated with MPZ mutations has been described. We report six patients (one sporadic case and five subjects from two apparently unrelated families) with a late onset, but rapidly progressive, axonal peripheral neuropathy. In all patients, molecular analysis demonstrated a novel heterozygous missense mutation (208C>T) in MPZ exon 2, causing the Pro70Ser substitution in the extracellular domain. The diagnosis of CMT2 associated with MPZ mutations should be considered in both sporadic and familial cases of late onset, progressive polyneuropathy. The mechanism whereby compact myelin protein mutations cause axonal neuropathy remains to be elucidated.

Neurovascular decompression in trigeminal neuralgia: role of intraoperative neurophysiological monitoring in the learning period.

This paper deals with the first 45 consecutive patients undergoing microvascular decompression (MVD) surgery for trigeminal neuralgia, studied with perioperative brainstem auditory evoked potentials (BAEPs) and electromyography (EMG). We observed a good correlation between the intraoperative BAEP modifications and postoperative hearing function. BAEP monitoring was useful in identifying the manoeuvres that may compromise cochlear nerve function. This improved the surgical technique in the subsequent cases and reduced the incidence of iatrogenic hearing deficits after the learning period. There were no correlations between the entity of the intraoperative EMG discharges and the postoperative facial and trigeminal function. Intraoperative EMG monitoring can be useful during the period of learning as a means of identifying the different nerves in the cisternal tract.

Unusual neurophysiological and immunological findings in myasthenia gravis: a case report.

We describe the case of a male patient with ocular myasthenia gravis who developed a diabetic neuropathy similar to chronic inflammatory demyelinating polyradiculoneuropathy associated with transient generalized 'myokymic' discharges and distal weakness. He had antibodies against acetylcholine receptor and GQ1b ganglioside, but not anti-voltage-gated K(+) channel antibodies. Serial electrophysiological and immunological findings showed that diabetes was involved in the immune-mediated mechanism of peripheral neuropathy. We hypothesize that the concomitant appearance of distal motor weakness and decreased compound muscle action potentials upon repetitive nerve stimulation, together with increased distal motor latency and generalized peripheral nerve hyperexcitability, were all related to transient serum positivity to anti-GQ1b antibodies.