Garrett E. Alexander

Primary Sjögren's Syndrome with Central Nervous System Disease Mimicking Multiple Sclerosis

Central nervous system involvement has occurred in approximately 20% of patients with primary Sjögrens syndrome evaluated at our institution. Characteristically, the neurologic dysfunction is multifocal, involving both the brain and spinal cord, and is recurrent over time. We present the features of 20 patients with primary Sjögrens syndrome and central nervous system involvement whose neurologic findings, evoked potential abnormalities, and cerebrospinal fluid profiles (elevated IgG indices, oligoclonal bands on agarose gel electrophoresis, and mild pleocytosis with reactive lymphoid cells) closely resembled those of multiple sclerosis. In fact, multiple sclerosis was considered the most likely diagnosis in each of these patients before diagnosis of Sjögrens syndrome, and each patient met criteria for definite multiple sclerosis. The clinical effects of corticosteroid treatment during episodes of acute neurologic dysfunction appeared to be beneficial in these patients.

Do cortical and basal ganglionic motor areas use motor programs to control movement

Prevailing engineering-inspired theories of motor control based on sequential/algorithmic or motor-programming models are difficult to reconcile with what is known about the anatomy and physiology of the motor areas. This is partly because of certain problems with the theories themselves and partly because of features of the cortical and basal ganglionic motor circuits that seem ill-suited for most engineering analyses of motor control. Recent developments in computational neuroscience offer more realistic, that is, connectionist, models of motor processing. The distributed, highly parallel, and nonalgorithmic processes in these models are inherently self-organizing and hence more plausible biologically than their more traditional algorithmic or motor-programming counterparts. The newer models also have the potential to explain some of the unique features of natural, brain-based motor behavior and to avoid some of the computational dilemmas associated with engineering approaches.

Sjögren syndrome Central nervous system manifestations

we studied eight patients who had primary Sjogren syndrome and central nervous system (CNS) disorders that were not attributable to other causes. Focal cerebral deficits were observed in five patients. Aseptic meningoencephalitis was seen in five patients, recurrent in one. Spinal cord manifestations in three patients took several forms: acute transverse myelitis, chronic progressive myelopathy, and spinal subarachnoid hemorrhage. Precipitating antibodies to the Ro(SSA) cytoplasmic antigen were detected in the sera of seven of eight patients. This may be relevant to the pathogenesis of CNS disease in Sjogren syndrome, because there is a strong correlation between vasculitis and the presence of anti-Ro(SSA) antibodies in this connective tissue disorder.

Neurologic Complications of Primary Sj??gren??s Syndrome

Although peripheral nervous system disease has been well documented in Sjögrens syndrome (SS), central nervous system (CNS) involvement is considered distinctly uncommon. Sixteen patients with primary SS and CNS disorders not attributable to other causes were the subjects of this study. Cerebral manifestations, both focal and diffuse, as well as spinal cord disease, were observed. Peripheral vasculitis occurred in 12 patients (75%), 83% of whom had anti-Ro(SSA) antibodies. The high proportion of patients with concomitant peripheral vasculitis, and the observed association with antibodies to the Ro(SSA) antigen system which, in other studies, has been linked to vasculitis in SS, suggest that an immune vasculopathy may play a role in the pathogenesis of the CNS disease of SS.

Aseptic meningoencephalitis in primary Sjogren's syndrome

The (clinical features and CSF characteristics of five patients with primary Sjogrens syndrome (SS) and associated aseptic meningoencephalitis (AME) are described. Episodes of AME were recurrent in four patients. Viral, fungal, and bacterial cultures were uniformly negative. Plasma cells were observed in the CSF but not in the blood of three patients. The CSF 1gG:albumin index was elevated, suggesting intrathecal synthesis of IgG in each of the four patients tested; each patient had either one or two broad bands with the mobility of IgG on CSF agarose electrophoresis. These observations are consistent with current understanding of SS as a polyclonal gammopathy associated with the multifocal proliferation of B lymphocytes and plasma cells.

Temporal profile of improvement of tardive dystonia after globus pallidus deep brain stimulation.

BACKGROUNDnSeveral case reports and small series have indicated that tardive dystonia is responsive to globus pallidus deep brain stimulation. Whether different subtypes or distributions of tardive dystonia are associated with different outcomes remains unknown.nnnMETHODSnWe assessed the outcomes and temporal profile of improvement of eight tardive dystonia patients who underwent globus pallidus deep brain stimulation over the past six years through record review. Due to the retrospective nature of this study, it was not blinded or placebo controlled.nnnRESULTSnConsistent with previous studies, deep brain stimulation improved the overall the Burke-Fahn-Marsden motor scores by 85.1 ± 13.5%. The distributions with best responses in descending order were upper face, lower face, larynx/pharynx, limbs, trunk, and neck. Patients with prominent cervical dystonia demonstrated improvement in the Toronto Western Spasmodic Torticollis Rating Scale but improvements took several months. In four patients the effects of deep brain stimulation on improvement in Burke Fahn Marsden score was rapid, while in four cases there was partial rapid response of neck and trunk dystonia followed by was gradual resolution of residual symptoms over 48 months.nnnCONCLUSIONnOur retrospective analysis shows excellent resolution of tardive dystonia after globus pallidus deep brain stimulation. We found instantaneous response, except with neck and trunk dystonia where partial recovery was followed by further resolution at slower rate. Such outcome is encouraging for using deep brain stimulation in treatment of tardive dystonia.

Control of goal-directed limb movements in primates: neurobiological evidence for parallel, distributed motor processing

Publisher Summary The control of goal-directed limb movements requires that the target or goal of each movement be translated quickly and efficiently into an appropriate set of muscle activation patterns that will carry the limb along the required trajectory. The control of goal-directed limb movements in three-dimensional space represents an enormously complex challenge to the motor system. Theorists have embraced the concept of the motor program in an attempt to account for the remarkable speed and flexibility of skilled motor behaviors. However, fundamental issues regarding the origin and nature of motor programs have yet to be addressed in detail. This chapter focuses on the parallel distributed processing (PDP) models of motor control, which represent an exciting new approach to the study of the neural substrates of motor behavior. Such models provide detailed and testable hypotheses concerning the neural basis for the complex and highly adaptive motor behavior of primates. Recent neurophysiological investigations of the motor system in awake, behaving primates have shown that each of three interconnected motor areas contains neural representations of several different levels of motor processing. The concept of parallel distributed motor processing represents an important theoretical advance in the study of the neural control of movement. PDP approaches to neural modeling will very likely provide the first detailed, testable, and neurobiologically relevant models of motor processing in primates.