Two women with typical stiff-man syndrome (SMS) developed increasingly frequent attacks of muscle spasms with severe paroxysmal autonomic dysfunctions such as transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary dilation, and arterial hypertension. Autoantibodies to GABA-ergic neurons were identified in the serum of both patients and in the cerebrospinal fluid of one. Both died suddenly and unexpectedly. General autopsy did not reveal the cause of death. Neuropathological studies revealed perivascular gliosis in the spinal cord and brain stem of one patient and lymphocytic perivascular infiltration in the spinal cord, brain stem, and basal ganglia of the other. The occurrence of a chronic inflammatory reaction in one of the two patients supports the idea that an autoimmune disease against GABA-ergic neurons may be involved in SMS. A review of the literature indicates that functional impairment in SMS is severe and prognosis is unpredictable because of the potential for sudden and unexpected death. Both muscular abnormalities and autonomic dysfunctions may result from autoimmunity directed against GABA-ergic neurons.

Maternal infection is a shared environmental risk factor for a spectrum of neuropsychiatric disorders and animal models of maternal immune activation (MIA) exhibit a range of neuropathologies and behaviors with relevance to these disorders. In particular, MIA offspring show chronic, age-and region-dependent changes in brain cytokines, a feature seen in postmortem studies of individuals with neuropsychiatric disorders. These MIA-induced alterations in brain cytokines may index biological processes underlying progression to diagnosable neuropsychiatric disorders. However, cytokines signal through specific cytokine receptors to alter cellular processes and it is the levels of those receptors that are critical for signaling. Yet, it remains unknown whether MIA alters the expression of cytokine receptors in the brains of offspring throughout postnatal development. Here, we measured the expression of 23 cytokine receptors in the frontal cortex of MIA and control offspring from birth to adulthood using qPCR. MIA offspring show dynamic oscillating alterations in cytokine receptors during sensitive periods of neural growth and synaptogenesis. Of the many cytokine receptors altered in the FC of MIA offspring, five were significantly changed at multiple ages at levels over 2-fold relative to controls-Il1r1, Ifngr1, Il10ra, Cx3cr1 and Gmcsfrsuggesting persistent dysfunction within those pathways. In addition to facilitating immune responses, these cytokine receptors play critical roles in neuronal migration and maturation, synapse formation and elimination, and microglial function. Together with previously reported changes in cytokine levels in the brains of MIA offspring, our results show a decrease in cytokine signaling during the peak period of synaptogenesis and spine formation and an increase during periods of activity-dependent development Principal component loadings for P1 and PC2 P60 P7 P0 P14 P30

This 3-month-old Caucasian boy, son of nonconsanguineous parents was seen by us for evaluation of microcephaly. His 16-year-old mother smoked during pregnancy but did not consume alcohol or drugs. At 16 wk gestation, she was in a car accident and was "tossed around a lot," but did not sustain any obvious injuries. At about the same time she developed a sore throat with cervical lymph node swelling.The infant was born 3 wk post-term by cesarean section, done for face presentation. Microcephaly was noted at birth. At the time of evaluation, head circumference was below the third centile, while length and weight were normal. As seen in Figure la, b, he had a sloping forehead, prominent occiput, nearly closed sutures with ridging, bitemporal grooving, posteriorly angulated ears, micrognathia, and prominent nasal bridge with wide-set eyes. No other systemic abnormalities were present.Neurologically, the infant was severely delayed in psychomotor development, unable to see or hear, had optic atrophy, feeding problems, spasticity of all limbs, and episodes of opisthotonic arching and infantile spasms. Skull films confirmed that most of the sutures were closed. CT scan showed reduced number of sulci and gyri, with failure of opercularization of the insula and partial absence of the septum pellucidum. Calcification was noted in the periventricular region. A burst-suppression pattern was seen on EEG. Results of high-resolution chromosome studies and thyroid and adrenal function tests were normal. He had chronic hyponatremia, which was considered to be due to osmoregulator dysfunction. Spinal fluid examination, serology, and TORCH titers were normal.

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