Heterogeneity of lung disease associated with NK2 homeobox 1 mutations.

We retrospectively studied the clinical presentation, treatment modalities and outcome in 16 patients with heterozygous NKX2-1 mutation associated with chronic lung disease. Twelve different NKX2-1 mutations, including 4 novel mutations, were identified in the 16 patients. Nine patients presented with brain-lung-thyroid syndrome, 3 had neurological and lung symptoms and 4 had only pulmonary symptoms. Ten patients had neonatal respiratory distress, and 6 of them developed infiltrative lung disease (ILD). The other patients were diagnosed with ILD in childhood (n = 3) or in adulthood (n = 3). The median age at diagnosis was 36 months (IQ 3.5-95). Patient testing included HRCT (n = 13), BALF analysis (n = 6), lung biopsies (n = 3) and lung function tests (n = 6). Six patients required supplemental oxygen support with a median duration of 18 months (IQ 2.5-29). All symptomatic ILD patients (n = 12) benefited from a treatment consisting of steroids, azithromycin (n = 9), and/or hydroxychloroquine (n = 4). The median follow-up was 36 months (IQ 24-71.5). One patient died of respiratory failure at 18 months and another is waiting for lung transplantation. In summary, the initial diagnosis was based on clinical presentation and radiological features, but the presentation was heterogeneous. Definitive diagnosis required genetic analysis, which should be performed, even in absence of neurological or thyroid symptoms.

Action selection in a possible model of striatal medium spiny neuron dysfunction: behavioral and EEG data in a patient with benign hereditary chorea.

Chaining or cascading of different actions and responses is necessary to accomplish a goal. Yet, little is known about the functional neuroanatomical-electrophysiological mechanisms mediating these processes. Computational models suggest that medium spiny neurons (MSNs) play an important role in action cascading, but this assumption has hardly been tested relating neuroanatomical and electrophysiological parameters in a human model of circumscribed MSN dysfunction. As a possible human model of circumscribed MSN dysfunction, we investigate benign hereditary chorea in a case-control study applying bootstrap statistics. To investigate these mechanisms, we used a stop-change paradigm, where we apply mathematical constraints to describe the degree of how task goals are activated with more or less overlap during action cascading. We record event-related potentials and analyze neural synchronization processes. The results show that MSN dysfunctions lead to deficits in action cascading processes only when two response options seek simultaneous access to response selection resources. Attentional selection processes are not affected, but processes reflecting the transition between stimulus evaluation and responding are affected. The results underline computational models of MSN functioning and show that dysfunction in these networks leads to a more parallel and hence inefficient response selection.

The thalamic ultrastructural abnormalities in paroxysmal kinesigenic choreoathetosis: a diffusion tensor imaging study.

Paroxysmal kinesigenic choreoathetosis (PKC) is a rare neurologic disorder. There are not apparent morphological changes in patients with idiopathic PKC. The purpose of this study is to determine whether ultrastructural changes are in the brain of patients with idiopathic PKC using diffusion tensor imaging. From May 2007 to August 2008, seven patients with idiopathic PKC were included. The mean age at initial onset was 11.7 +/- 3.1 (range 8-17) years, and the mean disease duration was 6.9 +/- 5.1 (range 1-14) years. Seven subjects of an age- and sex-matched control group were recruited. DTI data were obtained with a 3-T scanner. Fractional anisotropy (FA) and mean diffusivity (MD) were obtained in eight brain regions of interest. Patients with idiopathic PKC had significantly higher FA values than controls in the right thalamus (P < 0.05 Bonferroni corrected). Patients also had lower MD values than controls in the left thalamus (P < 0.05 Bonferroni corrected). FA and MD values were not significantly correlated with age of onset, gender, frequency of attack and duration of the disease. The results showed that in patients with idiopathic PKC, diffusion tensor imaging discloses distinct ultrastructural abnormalities in the thalamus. DTI is a sensitive neuroradiologic technique for detecting cerebral alterations in patients even without visible lesions on conventional MRI.

Complete suppression of paroxysmal nonkinesigenic dyskinesia by globus pallidus internus pallidal stimulation.

Stereotactic functional surgery is being explored as potential therapies for medically intractable paroxysmal dyskinesias (PxD). We report on a 59-year-old man in whom stimulation of globus pallidus internus produced immediate and sustained relief of paroxysmal non-kinesigenic dyskinesia secondary to a rotator cuff tears on the left shoulder. Our finding strongly suggests that altered function of neuronal circuits of the basal ganglia underlies the manifestation of PxD.

Diagnostic role of 99mTc hexamethyl-propyleneamine oxime brain single photon emission computed tomography in Sydenham's chorea.

BACKGROUND: The objective of this study was to determine whether technetium-99m hexamethyl-propyleneamine oxime (HMPAO) brain single photon emission computed tomography (SPECT) imaging is capable of detecting perfusional abnormalities in Sydenham's chorea (SC) patients and contributing to diagnosis of SC. METHODS: In this study, 17 SC patients were evaluated. HMPAO SPECT was performed on all patients at the acute phase and six of them at the recovery phase. Magnetic resonance imaging (MRI) of the brain was performed to 13 patients. SPECT images of basal ganglia and thalamus were evaluated both visually and by measuring the radioactivity uptakes. Ten subjects constituted the control group. RESULTS: HMPAO SPECT was visually evaluated as indicating hyperperfusion in the basal ganglia and thalamus in 16 patients, and evaluated as normal in one patient at the acute phase. The radioactivity uptakes of basal ganglia and thalamus of the patients at the acute phase were found statistically higher than those of the patients at the recovery phase, and also higher than those of the control group (P < 0.05). A significant difference between the radioactivity uptake of the patients at the recovery phase and those of the control group was not found (P > 0.05). Only one patient did not show any abnormality in both acute and recovery phases. MRI study did not show any abnormality in the basal ganglia and thalamus. CONCLUSION: It is suggested that brain SPECT can contribute to the diagnosis of SC as an objective tool. Resolving of the hyperperfusion at the recovery phase provides further support for the diagnosis of SC.

Minimal tissue damage after stimulation of the motor thalamus in a case of chorea-acanthocytosis.

Autopsy findings are reported from a patient with chorea-acanthocytosis treated for 2 years by deep brain stimulation (DBS) of the motor thalamus. Postoperative testing showed a progressive improvement in axial truncal spasms. Although relatively high currents were used for 2 years in this patient, postmortem analysis showed minimal tissue damage in the vicinity of the electrode tip. It is concluded that DBS has little impact on the surrounding tissues.

Chorea-acanthocytosis: neuropathology of brain and peripheral nerve.

We report the neuropathological data from a familial case of chorea-acanthocytosis with central and peripheral nervous system involvement. At the age of 34, the patient underwent a peripheral nerve biopsy which was analyzed by light- and electron microscopy. These studies showed a selective reduction in the large diameter myelinated fibre population, with several clusters of regeneration. Remyelinating fibers surrounded by flattened Schwann cell processes were also present. The patient died at the age of 44, and post-mortem macroscopic examination of the brain showed marked atrophy of the caudate. Histological examination of paraffin sections showed almost complete depletion of neurons in the caudate, with severe astrocytic gliosis. The putamen and pallidum were slightly less severely depleted of neurons, but with marked astrocytic gliosis. Diffuse mild gliosis was also evidenced, by immunohistochemistry with anti-GFAP, in the thalamus and subcortical white matter.