Spontaneous Intracranial Hypotension Presenting With Frontotemporal Dementia: A Case Report

Spontaneous intracranial hypotension (SIH) is a rare and often underdiagnosed condition, which commonly results from a cerebrospinal fluid leak. The classic clinical presentation of SIH is a postural headache and dizziness. Less frequent complications include nausea, neck stiffness, and even coma. This case report describes a 70-year-old woman with an initial complaint of postural headaches and sleep attacks, who developed a 22-month progressive history of personality and behavioral changes, cognitive decline, urinary incontinence, chorea, and dysarthria. Although no specific cerebrospinal fluid leak was identified, the patient was suspected of having SIH and her symptoms completely reversed after a 2-month course of steroids. This case highlights that SIH represents a rare and reversible cause of a wide spectrum of neurological symptoms, including dementia. Neurologists should be aware of this diagnosis when evaluating patients with neurological signs and symptoms that cannot otherwise be explained

Transient, Recurrent Central Nervous System Clinical Manifestations of X-Linked Charcot-Marie-Tooth Disease Presenting with Very Long Latency Periods between Episodes: Is Prolonged Sun Exposure a Provoking Factor?

Charcot-Marie-Tooth disease is one of the most common inherited neurological disorders affecting the peripheral nervous system. The common clinical manifestations of the disease are distal muscle weakness and atrophy, often associated with a characteristic steppage gait and foot deformities. Transient acute and recurrent or chronic central nervous system manifestations, predominantly, dysarthria, dysphagia, motor weakness, and ataxia, have been recognized as a feature of the X-linked type 1 of CMT (CMTX1). The CNS symptoms occur typically in young age and often precede the clinical manifestation of the polyneuropathy. Several predisposing factors such as exercise, fever, and returning from areas of high altitude have been described as triggers of the CNS symptoms; however, in many cases, a substantial cause remains undetermined. In this report, we describe a patient with three attacks of transient CNS deficits at the ages of 11, 21, and 38 years, respectively, which were also accompanied by transient white matter abnormalities on MRI. Two of the attacks occurred after prolonged exposure to sunlight. In our knowledge, this is the first documented case with such long latency periods between CNS attacks as well as the only report describing intense sun exposure as a possible provoking factor

Clinical Utility of Functional RNA Analysis for the Reclassification of Splicing Gene Variants in Hereditary Cancer

Background: Classification of splicing variants (SVs) in genes associated with hereditary cancer is often challenging. The aim of this study was to investigate the occurrence of SVs in hereditary cancer genes and the clinical utility of RNA analysis. Material and Methods: 1518 individuals were tested for cancer predisposition, using a Next Generation Sequencing ( NGS) panel of 36 genes. Splicing variant analysis was performed using RT-PCR and Sanger Sequencing. Results: In total, 34 different SVs were identified, 53% of which were classified as pathogenic or likely pathogenic. The remaining 16 variants were initially classified as Variant of Uncertain Significance (VUS). RNA analysis was performed for 3 novel variants. Conclusion: The RNA analysis assisted in the reclassification of 20% of splicing variants from VUS to pathogenic. RNA analysis is essential in the case of uncharacterized splicing variants, for proper classification and personalized management of these patients