The ventral striatum is considered to be that portion of the striatum associated with the limbic system by virtue of its afferent connections from allocortical and mesolimbic areas as well as from the amygdala. The efferent projections from this striatal region in the primate were traced by using 3H amino acids and Phaseolus vulgaris-leucoagglutinin (PHA-L). Particular attention was paid to the topographic organization of terminal fields in the globus pallidus and substantia nigra, the projections to non-extrapyramidal areas, the relationship between projections from the nucleus accumbens and the other parts of the ventral striatum, and the comparison between ventral and dorsal striatal projections. This study demonstrates that in monkeys a circumscribed region of the globus pallidus receives topographically organized efferent fibers from the ventral striatum. The ventral striatal fibers terminate in the ventral pallidum, the subcommissural part of the globus pallidus, the rostral pole of the external segment, and the rostromedial portion of the internal segment. The more central and caudal portions of the globus pallidus do not receive this input. This striatal output appears to remain segregated from the dorsal striatal efferent projections to pallidal structures. Fibers from the ventral striatum projecting to the substantia nigra are not as confined to a specific region as those projecting to the globus pallidus. Although the densest terminal fields occur in the medial portion, numerous fibers also extend laterally to innervate the dorsal stratum of dopaminergic neurons of the substantia nigra and the retrorubral area. Furthermore, they project throughout the rostral-caudal extent of the substantia nigra. Projections from the medial part of the ventral striatum reach the more caudally located pedunculopontine tegmental nucleus. Thus unlike the above described terminals in the globus pallidus, the ventral striatum project widely throughout the substantia nigra, a fact that indicates that they may contribute to the integration between limbic and other output systems of the striatum. Finally, the ventral striatum projects to non-extrapyramidal regions including the bed nucleus of the stria terminals, the nucleus basalis magnocellularis, the lateral hypothalamus, and the medial thalamus.
Background: Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension.Objective: To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo.
Design:We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given.Results: No significant differences were seen in the supine BP, either systolic (P=.36) or diastolic (P=.85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P=.02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P=.04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P=.002). Standing BP improvement significantly regressed with improvement in OH symptoms.Conclusions: Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.
We analyzed the clinical characteristics of 18 patients (13 female, 5 male) who had autoimmune autonomic neuropathy (AAN) and ganglionic acetylcholine receptor (AChR) autoantibodies. Mean age was 61.4 years (standard deviation, 12.0 years). Ten patients had subacute symptom onset, six with an antecedent event. Eight patients had chronic AAN, characterized by insidious symptom onset, without antecedent event, and gradual progression. A majority of patients with high antibody values (>1.00 nmol/L) had a combination of sicca complex (marked dry eyes and dry mouth), abnormal pupillary light response, upper gastrointestinal symptoms, and neurogenic bladder. Chronic AAN segregated into two subgroups. One subgroup (N = 4) had low antibody titer (0.09 +/- 0.01 nmol/L) and a paucity of cholinergic symptoms. It was indistinguishable from pure autonomic failure. The other subgroup (N = 4) had high antibody titer (11.6 +/- 2.08 nmol/L), sicca complex, abnormal pupils, and neurogenic bladder; three had severe upper gastrointestinal dysfunction. Higher antibody titers correlated with greater autonomic dysfunction and more frequent cholinergic dysautonomia. These observations expand the clinical spectrum of AAN to include chronic cases, some being indistinguishable from pure autonomic failure, and support the concept that ganglionic AChR antibodies are important diagnostically and pathophysiologically in acquired dysautonomia.
Adult polyglucosan body disease is a clinicopathologic entity characterized by progressive upper and lower motor neuron dysfunction, sensory loss in the lower extremities, sphincter dysfunction, and occasionally dementia. Pathologically, numerous large polyglucosan bodies are noted in peripheral nerves, cerebral hemispheres, and the spinal cord, as well as in other systemic tissues. We present a case of probable adult polyglucosan body disease based on clinical history and examination, magnetic resonance images, and sural nerve biopsy findings.
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