The recent identification of the transactive response DNA binding protein with a molecular weight of 43 kDa (TDP-43) as the major pathological protein, in both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin positive inclusions (FTLD-U), provides the new insight into understanding disease processes. The pathogenesis of both diseases is unclear, although they are related by having some overlap of symptoms and now by the shared histopathology of TDP-43 deposition. The number of degenerative diseases associated with TDP-43 has increased, leading to the new designation "TDP-43 proteinopathy". TDP-43 is a highly conserved protein ubiquitously expressed in many tissues including the central nervous system where it is present in neuronal and glial nuclei and to a lesser extent in the cytoplasm. Currently, TDP-43 has been implicated in regulating gene transcription and alternative splicing, in addition to maintaining mRNA stability. However, we still need to investigate the effects of posttranslational modifications of TDP-43, including phosphorylation, ubiquitination, and cleavage, on its regulation of various cellular processes. We review recently published studies of TDP-43 and its relationship to human disease with a special focus on ALS and FTLD-U. We conclude that the TDP-43 proteinopathies represent a novel class of neurodegenerative disorders and both ALS and FTLD-U are closely related conditions linked to similar mechanism of neurodegeneration.
Alternative Splicing ; Amyotrophic Lateral Sclerosis ; Central Nervous System ; Cytoplasm ; DNA ; DNA-Binding Proteins ; Frontotemporal Dementia ; Frontotemporal Lobar Degeneration ; Humans ; Molecular Weight ; Neurodegenerative Diseases ; Neurons ; Phosphorylation ; Protein Processing, Post-Translational ; RNA Stability ; TDP-43 Proteinopathies ; Ubiquitin ; Ubiquitination

BACKGROUND: Atrial fibrillation (AF), commonly considered as a cardiac embolic source, can itself be induced by stroke. We therefore tried to find and analyze this 'stroke-induced' AF. METHODS: From the Inha University Stroke Registry of the past 2 years, 143 middle cerebral artery (MCA) territorial infarct patients who had been admitted within 48 hours after stroke onset were recruited to participate in the study. Electrocardiograms (EKG) on admission and follow-up during hospitalization were analyzed. Also, MCA infarct was subdivided according to insular involvement by brain imaging. RESULTS: Among 143 MCA territorial infarcts, 38 patients had AF on admission (Rt:21; Lt:17). Of those, insular involvements of the MCA infarct was noted in 32 patients. All the patients had a follow-up EKG and AF disappeared in 3 patients (Rt:2; Lt:1). In the remaining 105 patients, 10 patients subsequently developed new AF within 1 week after hospitalization. All those 10 patients had right-sided MCA infarcts and insular involvements were present in 9 patients. In summary, among the 48 MCA infarct associated with AF, 13 AF (Rt:12; Lt:1) were presumed to be the consequence and not the cause of stroke. CONCLUSIONS: Though human insular stimulation and inactivation studies have suggested that AF would be more common in left insular destructive lesions, it was not always supported in clinical series. From our study, presumed 'stroke-induced' AF was highly associated with right insular lesions. The mechanism of arrhythmogenesis by ischemic stroke might be more complicated than previously expected and, not merely the simple inactivation of an anatomical substrate, the insular cortex.
Atrial Fibrillation* ; Electrocardiography ; Follow-Up Studies ; Hospitalization ; Humans ; Middle Cerebral Artery* ; Neuroimaging ; Stroke

Transcranial direct current stimulation (tDCS) is non-invasive brain stimulation technique increasingly used for modulation of central nervous system excitability in humans. The use of non-invasive brain stimulation has significant advantages, such as not involving surgical procedures and having relatively mild adverse effects. In recent years there has been an exponential rise in the number of studies employing tDCS as a means of gaining an improvement on motor and cognitive function in patients with neurological diseases. In the present review, we will first introduce a brief background on the basic principles of tDCS. We also summarize recent studies with tDCS that aimed at enhancing behavioral outcome or disease-specific symptoms in patients suffering from stroke, movement disorders, Alzheimer disease, and epilepsy. Although outcomes of tDCS trials include some conflicting results, the evidence supports that tDCS might have a therapeutic value in different neurological conditions.
Alzheimer Disease ; Brain ; Central Nervous System ; Cognition ; Epilepsy ; Humans ; Movement Disorders ; Nervous System Diseases* ; Stroke ; Transcranial Direct Current Stimulation*

A 26-year-old woman presented with skin pigmentation and numbness on the upper arm. More than six café au lait spots over 15 mm diameter could be seen throughout her skin. Neurofibromatosis (NF) type 1 was diagnosed based on genetic study. The brain magnetic resonance imaging (MRI) showed Chiari type 1 malformation and syringomyelia was noted in the C2 to T7 level in the spinal MRI. We suggest Chiari malformation and syringomyelia could be a rare manifestation in a patient with NF type 1.

Bilateral striopallidodentate calcinosis involves calcification of the basal ganglia and dentate nuclei of the cerebellum. On occasion it may be associated with either hypoparathyroidism or pseudohypoparathyroidism. We report a 52-year-old woman with enduring dysarthria. She had bilateral calcification of the basal ganglia, thalamus, and dentate nuclei on a brain CT. She also had hypothyroidism. Familial study including her son and daughter was negative. We emphasize the need to evaluate the thyroid function in patients with specific intracranial calcifications.
Basal Ganglia ; Brain ; Calcinosis* ; Cerebellum ; Dysarthria ; Female ; Humans ; Hypoparathyroidism ; Hypothyroidism* ; Middle Aged ; Nuclear Family ; Pseudohypoparathyroidism ; Thalamus ; Thyroid Gland

Hypertensive encephalopathy is a medical emergency whose clinical manifestations are usually associated with bilateral parieto-occipital lesions. Predominant brainstem edema without accompanying occipital lesions is rare in hypertensive encephalopathy and usually occurs in patients with secondary hypertension. We describe the clinical and radiological features of two patients with reversible hypertensive brainstem encephalopathy. Both patients had chronic renal failure, but the extensive neuroimaging abnormalities revealed few clinical features of brainstem involvement. The clinical findings and neuroimaging abnormalities resolved once the hypertension was treated.
Brain Stem* ; Edema ; Emergencies ; Humans ; Hypertension ; Hypertensive Encephalopathy* ; Kidney Failure, Chronic ; Neuroimaging

Pancreatic encephalopathy is a rare complication of acute pancreatitis. We report a 80-year-old woman who, after an acute episode of pancreatitis, developed a fluctuating confusion and clouded consciousness. She experienced two relapses with alternating encephalopathic features. Serum amylase was highly increased and symptoms were relieved in accord with normalized amylase value. We suggest that this encephalopathic features may be related with pancreatitis.
Aged, 80 and over ; Amylases ; Consciousness ; Female ; Humans ; Pancreatitis* ; Recurrence

BACKGROUND: The terminal latency index (TLI) is a calculated value that adjusts the distal motor latency for the terminal distance and the proximal motor nerve conduction velocity. The purpose of this study is to evaluate the sensitivity of the median TLI in the diagnosis of carpal tunnel syndrome (CTS) and compare it with other electrophysiological parameters. METHODS: We prospectively studied 32 patients with nerve conduction studies using a conventional surface technique in the median and ulnar nerves. The distal distance for the CMAP was measured in 5 cm using Oh's techniques. Based on the clinical diagnosis, 32 patients (59 hands) were judged to have CTS. Control data were obtained from 40 healthy hands utilizing identical techniques. RESULTS: The mean TLI was 0.24 +/- 0.04 in the CTS group and 0.30 +/- 0.02 in the control group (P<0.01). The 32 patients had a mean age of 57 years (SD +/- 13 years; 73% women). Twenty subjects with an average age of 46 years (SD +/- 15 years; 65% women) were evaluated for control data. The calculated lower limit of normal from the control group (mean-2SD) was 0.26. The sensitivity of the TLI was 73%. The TLI was statistically better than the median motor distal latency and sensory nerve conduction velocity in the second digit-wrist segment. In four patients from the CTS group, the TLI was the only abnormal electrophysiological parameter. CONCLUSIONS: The median TLI is an easy, inexpensive, highly informative test and is therefore extremely useful in the diagnostic work-up of patients with CTS.
Carpal Tunnel Syndrome* ; Diagnosis ; Hand ; Humans ; Median Nerve* ; Neural Conduction ; Prospective Studies ; Reference Values* ; Ulnar Nerve

There is an increasing number of reports that the lesion site in isolated cranial neuropathies may be the brainstem. The authors describe a diabetic patient with peripheral type facial palsy and concurrent trochlear palsy. Magnetic resonance imaging showed only a small pontine infarction responsible for the facial palsy. Multiple cranial nerve palsies seen in this patient might be a manifestation of multiple acute small infarcts involving both the brainstem and its cranial nerve root simultaneously.
Brain Stem ; Brain Stem Infarctions ; Cranial Nerve Diseases ; Cranial Nerves ; Diabetes Mellitus* ; Facial Paralysis ; Humans ; Infarction ; Magnetic Resonance Imaging ; Paralysis ; Trochlear Nerve Diseases* ; Trochlear Nerve*

BACKGROUND: It is important to consider leprosy as a cause of peripheral neuropathy, as it is readily treatable. We analyzed clinical and electrodiagnostic characteristics of leprosy patients with peripheral nerve involvement. METHODS: This study was a retrospective analysis of nerve conduction studies (NCS) and the medical records of 10 patients with leprosy were confirmed by a skin or nerve biopsy. NCS using a conventional surface technique were performed in 15 upper extremities and 14 lower extremities. RESULTS: Among ten patients, three patients presented with mononeuropathy, and the others with mononeuropathy multiplex. Five patients had medical histories of leprosy treatment. The patterns of peripheral neuropathies were mononeuropathy multiplex except for one who had an ulnar mononeuropathy. On motor NCS, low or absent CMAPs were most common abnormalities followed by slow conduction velocity and prolonged terminal latency. Sensory NCS also showed changes of amplitudes rather than in conduction velocity. The conduction block of CMAPs with or without dispersion were observed in 5 patients usually on the ulnar nerve at the forearm. CONCLUSIONS: In most instances, leprous patients with neuropathy presented with mononeuropathy multiplex affecting the sensory and motor nerves. NCS showed more likely axonal than demyelinating changes, but the conduction blocks were also found frequently at the forearms.
Axons ; Biopsy ; Forearm ; Humans ; Leprosy ; Lower Extremity ; Medical Records ; Mononeuropathies ; Neural Conduction ; Peripheral Nerves ; Peripheral Nervous System Diseases ; Retrospective Studies ; Skin ; Ulnar Nerve ; Upper Extremity