McLeod syndrome: Five new pedigrees with novel mutations.

OBJECTIVE: To present five new McLeod Syndrome (MLS) pedigrees with novel XK gene mutations, review the literature of this disorder, and discuss the typical and atypical clinical features noted with these new mutations. METHODS: This is a multi-center retrospective review of five MLS cases with novel gene mutations. Genotypic and phenotypic information has been obtained from each center. RESULTS: Five novel mutations are reported in this Case series. New clinical findings include prolonged asymptomatic elevated creatine kinase (CK) levels, vocal tics, presence of obstructive sleep apnea (OSA), and one patient of Vietnamese ethnicity. CONCLUSIONS: We expand on the clinical and genetic spectrum of MLS demonstrating the clinical variability of MLS.

Clinical vignettes in Parkinson's disease: a collection of unusual medication-induced hallucinations, delusions, and compulsive behaviours.

Hallucinations, delusions, and compulsive behaviors are frequent iatrogenic complications of the treatment of motor dysfunction in Parkinson's disease (PD). Although these have been studied, and the phenomenology described, there are few detailed descriptions of the various psychiatric problems our treated PD patients live with that allow physicians who do not have a great deal of experience with PD patients to appreciate the extent of their altered lives. This report is a compilation of vignettes describing these behavioral problems that the treating neurologist or psychiatrist attributed to the medications used for treating PD.

Inferior olive response to passive tactile and visual stimulation with variable interstimulus intervals.

The unique anatomical and electrophysiological features of the inferior olive and its importance to cerebellar function have been recognized for decades. However, understanding the exact function of the inferior olive has been limited by the general lack of correlation between its neural activity and specific behavioral states. Electrophysiological studies in animals showed that the inferior olive response to sensory stimuli is generally invariant to stimulus properties but is enhanced by unexpected stimuli. Using functional magnetic resonance imaging in humans, we have shown that the inferior olive is activated when subjects performed a task requiring perception of visual stimuli with unpredictable timing (Xu et al. J Neurosci 26(22):5990-5995, 2006, Liu et al. J Neurophysiol 100(3):1557-1561, 2008). In the current study, subjects were scanned while passively perceiving visual and tactile stimuli that were rendered unpredictable by continuously varying interstimulus intervals (ISIs). Sequences of visual stimuli and tactile stimuli to the right hand were presented separately within the same scanning session. In addition to the activation of multiple areas in the cerebellar cortex consistent with previous imaging studies, the results show that both tactile and visual stimulation with variable ISIs were effective in activating the inferior olive. Together with our previous findings, the current results are consistent with the electrophysiological studies in animals and further support the view that the inferior olive and the climbing fiber system primarily convey the temporal information of sensory input regardless of the modality.

Altered diffusion in the frontal lobe in Parkinson disease.

BACKGROUND AND PURPOSE: Parkinson disease (PD) is characterized by basal ganglia abnormalities. However, there are neurodegenerative changes in PD that extend beyond the basal ganglia and that are not sufficiently evaluated with standard MR imaging. The aim of this study was to characterize whole-brain gray matter (GM) and white matter (WM) changes in PD by using diffusion tensor imaging (DTI). MATERIALS AND METHODS: Thirteen control and 12 subjects with nondemented PD were examined by using DTI and 3D anatomic T1-weighted images. Statistical parametric mapping analyses of DTI and anatomic images were performed. Patients were evaluated with a variety of neurocognitive measures and the Unified Parkinson's Disease Rating Scale (UPDRS) OFF (cessation of medication) and ON (taking medications as normal) their antiparkinsonian medications. RESULTS: The PD participants had dopa-responsive features as ascertained by the UPDRS OFF versus ON medications and had no cognitive impairment. Decreased fractional anisotropy (FA) was observed in subjects with PD bilaterally in the frontal lobes, including the supplementary motor area, the presupplementary motor area, and the cingulum. There were no significant differences in mean diffusivity or GM/WM attenuation between PD subjects and controls. CONCLUSION: Statistical parametric mapping analysis of DTI showed changes in FA in frontal areas without volume loss. These results confirm that the neurodegenerative process extends beyond the basal ganglia in PD.

Selective impairments in implicit learning in Parkinson's disease.

The basal ganglia are thought to participate in implicit sequence learning. However, the exact nature of this role has been difficult to determine in light of the conflicting evidence on implicit learning in subjects with Parkinson's disease (PD). We examined the performance of PD subjects using a modified form of the serial reaction time task, which ensured that learning remained implicit. Subjects with predominantly right-sided symptoms were trained on a 12-element sequence using the right hand. Although there was no evidence of sequence learning on the basis of response time savings, the subjects showed knowledge of the sequence when performance was assessed in terms of the number of errors made. This effect transferred to the left (untrained) hand as well. Thus, these data demonstrate that PD patients are not impaired at implicitly learning sequential order, but rather at the translation of sequence knowledge into rapid motor performance. Furthermore, the results suggest that the basal ganglia are not essential for implicit sequence learning in PD.

The effect of subthalamic nucleus stimulation on kinaesthesia in Parkinson's disease.

BACKGROUND: Parkinson's disease is accompanied by deficits in passive motion and limb position sense. OBJECTIVE: To investigate whether deep brain stimulation of the subthalamic nucleus (STN-DBS) reverses these proprioceptive deficits. METHODS AND RESULTS: A passive movement task was applied to nine patients with Parkinson's disease and bilateral chronic STN-DBS and to seven controls. Thresholds for 75% correct responses were 0.9 degrees for controls, 2.5 degrees for Parkinson's disease patients when stimulation was OFF, and 2.0 degrees when stimulation was ON. CONCLUSIONS: STN-DBS improves kinaesthesic deficits in Parkinson's disease, but does not lead to a full recovery of proprioceptive function.

Dopamine agonists.

Dopamine agonists provide an effective means of treating early, middle, and late stages of Parkinson's disease. This article outlines the advantages and disadvantages of dopamine agonists as compared with levodopa therapy. The features and costs of the four Food and Drug Administration-approved agonists (bromocriptine, pergolide, pramipexole, and ropinirole) and apomorphine, another agonist presently under investigation, are discussed.

Hypertrophic olivary degeneration: metaanalysis of the temporal evolution of MR findings.

BACKGROUND AND PURPOSE: Hypertrophic olivary degeneration (HOD) is usually caused by a lesion in the triangle of Guillain and Mollaret and presents clinically as palatal tremor. Although the imaging features have been well described, the temporal course of hypertrophy and T2 signal increase in the inferior olivary nucleus (ION) has not been fully characterized. Our purpose was to evaluate the time course of MR imaging features of HOD caused by a lesion within the triangle of Guillain and Mollaret. METHODS: The temporal progression of HOD in 45 patients with symptomatic palatal tremor was obtained by extrapolation of combined MR imaging data from six patients treated at our institution and 39 patients reported in the literature. The MR examinations and reports were reviewed for presence of hyperintense signal in the ION on T2-weighted images, hypertrophy of the ION, and an inciting lesion in the triangle of Guillain and Mollaret. The interval between the MR examination and the inciting lesion was determined. RESULTS: Increased olivary signal on T2-weighted images first appeared 1 month after the inciting lesion and persisted for at least 3 to 4 years. Olivary hypertrophy initially developed 6 months after the acute event and resolved by 3 to 4 years. CONCLUSION: Visible changes on MR images in the ION in patients with a lesion in the triangle of Guillain and Mollaret correlate well with the described sequential histopathologic findings.

POEMS syndrome in a 24-year-old man associated with vitamin B12 deficiency and a solitary lytic bone lesion.

We report one of the youngest cases of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), presenting in a 24-year-old man. A solitary lytic bone lesion and vitamin B12 deficiency were also found. We suggest that this syndrome be considered in cases of subacute polyneuropathy developing in young adults.

High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor.

Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.

Recognition and management of shock in the pediatric patient.

Shock continues to be a challenge for health care professionals because shock is not a single pathologic process but a complex series of interrelated events. After respiratory failure, shock is the second most common cause of death in children. The etiology of shock can be classified into three major categories: hypovolemic, cardiogenic, and distributive shock (septic shock). Despite the etiology of the shock state, if left untreated, the overwhelming response of the body to the inadequate perfusion is death. The key to successful management and treatment of shock is early recognition and rapid intervention.

Atypical dopa responsive parkinsonism in a patient with megalencephaly, midbrain Lewy body disease, and some pathological features of Hallervorden-Spatz disease.

A 38 year old patient with megalencephaly, mental retardation, and lifelong tremor developed levodopa responsive parkinsonism in his mid-30s followed by the appearance of dyskinesiae, motor fluctuations, hallucinations, and dementia. Brain MRI showed, as well as other changes, iron deposition in the globus pallidus, substantia nigra, and the pulvinar of the thalamus. Postmortem examination disclosed depigmentation of the substantia nigra pars compacta with neuronal loss, gliosis, and Lewy body formation. Axonal dystrophic spheroids, neuronal loss, calcification, and iron deposition were found in the substantia nigra pars reticulata. Less severe changes without neuronal loss were seen in the globus pallidus. This combination of megalencephaly with neuroaxonal changes predominantly in the pars reticulata and Lewy body degeneration isolated to the substantia nigra pars compacta has not been previously reported.

Dopa-responsive parkinsonism phenotype of Machado-Joseph disease: confirmation of 14q CAG expansion.

The subtype IV of Machado-Joseph disease (MJD), characterized by parkinsonism variably combined with ataxia, distal atrophy, and sensory loss, has been all but ignored in recent reports of MJD, including those describing the molecular biologic substrate of the disease. We have demonstrated expansion of the CAG trinucleotide repeat of the MJD1 gene located on chromosome 14q32.1 in 2 patients of Azorean descent who presented with levodopa-responsive atypical parkinsonism. Previous publications have documented the presence of this expanded repeat in the other more common MJD phenotypes (I-III). To our knowledge, this is the first molecular biologic confirmation of the presence of the MJD1 gene in the subtype IV phenotype. Patients presenting with parkinsonism and peripheral neuropathy should be screened for this genetic defect.

Cerebral vein thrombosis due to hereditary antithrombin III deficiency.

Cerebral vein thrombosis, also called superior sagittal sinus thrombosis, is a well recognized clinical and radiologic entity associated with a variety of medical disorders. We report a patient with fatal cerebral vein thrombosis following myelography, in whom the cause was familial antithrombin III (AT3) deficiency. Unsuspected AT3 deficiency should be considered in cases of unexplained cerebral venous thromboses.

Reversible cortical blindness (Anton's syndrome) associated with bilateral occipital EEG abnormalities.

A 50-year-old woman with systemic lupus erythematosus was admitted in an obtunded state. An EEG recorded while she was unconscious demonstrated one episode of rhythmic sharp wave activity in the left occipital area that lasted for 5 minutes and was followed later in the same recording by an episode of high amplitude sharp wave discharges in the right posterior temporal and occipital areas. When the patient regained consciousness, she had an Anton's syndrome of cortical blindness with denial. When she recovered light perception only, the EEG demonstrated synchronous and independent right and left occipital-posterior temporal periodic lateralized epileptiform discharges (PLEDs). Cortical blindness (Anton's syndrome) associated with abnormal electrical activity in the occipital areas has only rarely been reported. Our case is significant for the following reasons: 1) PLEDs maximal right and left occipital areas associated with bilateral visual loss has not previously been observed; 2) abnormal electrical activity in the occipital lobes may be a reversible cause of Anton's syndrome.