Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, in which brain pathology is characterized by TDP-43 immunostaining. Through genome-wide linkage analysis we have identified five disease-segregating dynactin (DCTN1) CAP-Gly domain substitutions in 8 families that diminish microtubule binding and lead to intracytoplasmic inclusions. DCTN1 mutations were previously associated with motor neuron disease but can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders.

Objective-Autosomal dominant parkinsonism, hypoventilation, depression and severe weight loss (Perry syndrome) is an early-onset rapidly progressive disease. At autopsy, previous studies have found severe neuronal loss in the substantia nigra without Lewy bodies. Transactive response DNAbinding protein of 43 kDa (TDP-43) has recently been identified as a major ubiquitinated constituent of neuronal and glial inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis. This study reports clinical, genetic and neuropathologic investigations of Perry syndrome.Methods-Clinical data and autopsy brain tissue samples were collected from eight patients from four genealogically unrelated kindreds with Perry syndrome. Brain tissue was studied with immunohistochemistry and biochemistry for TDP-43. Patients were screened for mutations in the progranulin (GRN) and TDP-43 (TARDBP) genes.Results-The mean age at onset was 47 years (range: 40-56), and the mean age at death was 52 years (range: 44-64). In all patients, we identified TDP-43-positive neuronal inclusions, dystrophic neurites and axonal spheroids in a predominantly pallidonigral distribution, and we demonstrated changes in solubility and electrophoretic mobility of TDP-43 in brain tissue. The inclusions were highly pleomorphic and predominated in the extrapyramidal system, sparing the cortex, hippocampus and motor neurons. There were no mutations in GRN or TARDBP.Interpretation-Perry syndrome displays unique TDP-43 pathology that is selective for the extrapyramidal system and spares the neocortex and motor neurons.

Myokymia is a clinical phenomenon associated with characteristic electromyographic activity referred to as myokymic discharges. These are spontaneously generated bursts of individual motor unit potentials with each burst recurring rhythmically or semirhythmically, usually several times per second. It involves facial muscles more commonly than those of the extremities, and is most often seen in association with Guillain-Barré syndrome, multiple sclerosis, radiation plexopathy, pontine tumors, and timber rattlesnake envenomation. An alteration in the biochemical microenvironment of axon membranes at one of the various sites along the motor axon is the likely basis for the altered membrane excitability that underlies the myokymic discharges in most cases. The similarity of these discharges to those seen with hypocalcemic tetany, and the ability to manipulate myokymic discharges by altering serum-ionized Ca++, suggests that decrease in the ionized Ca++ in the microenvironment of the axon may play an important role.

Background and Purpose-The fornix connects various structures involved in memory. We report a patient with anterograde amnesia after an acute ischemic infarct in the anterior fornix. Case Description-A 71-year-old female with acute-onset amnesia had neuroimaging studies showing ischemic infarction of both columns and the body of the fornix and the genu of the corpus callosum. Neuropsychological evaluation revealed anterograde amnesia without evidence of callosal disconnection. The patient showed marked improvement in her memory function on the follow-up visit. Conclusions-Amnesia in this case is likely due to infarction of the anterior fornix structures.

Acute organophosphate intoxication resulting from suicide attempts in 14 patients produced a series of electrophysiologic abnormalities that correlated with the clinical course. Spontaneous repetitive firing of single evoked compound muscle action potentials (CMAP) was the earliest and most sensitive indicator of the acetylcholinesterase inhibition. A decrement of evoked CMAP following repetitive nerve stimulation was the most severe abnormality. At the height of the intoxication no CMAP was evoked after the first few stimuli. The decrement-increment phenomenon occurred only at milder stages of intoxication and its features are characteristic of acetylcholinesterase inhibition. These electrophysiologic features proved to be the most useful for determining initial severity and clinical course of the acute organophosphate intoxication and differentiated this syndrome from those of myasthenia gravis, Eaton-Lambert syndrome, and botulism.