A low-grade astrocytoma in a sixteen-year-old boy with a 7q11.22 deletion.

We report a patient with developmental delay due to germline AUTS2 mutation who developed a low-grade astrocytoma. While the contribution of this mutation to the pathogenesis of the tumor is not known at this time, a role of AUTS2 in deregulation of PRC1 can be a part in tumorigenesis of a brain tumor.

Efficacy of intrathecal baclofen on different pain qualities in complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by severe debilitating chronic pain. Patients with CRPS may experience various pain sensations, which likely embody different pathophysiologic mechanisms. In this study, we evaluated the differential effects of central γ-aminobutyric acid (B) receptor stimulation on the different pain qualities in CRPS patients with dystonia. METHODS: The 10 pain qualities of the neuropathic pain scale, dystonia severity, and changes in use of antinociceptive drugs were evaluated every 3 months for a period of 1 year in 42 CRPS patients with dystonia receiving titrated doses of intrathecal baclofen (ITB) treatment in an open design. RESULTS: Using a linear mixed model analysis and controlling for global dystonia severity and the use of supplemental analgesics, we found a significant improvement in global intense pain, sharp pain, dull pain, and deep pain during the first 6 months. After this period, the scores leveled off despite further improvement of dystonia and continued ITB dose escalation. CONCLUSIONS: γ-Aminobutyric acid (B) receptor stimulation by ITB exerts differential antinociceptive effects on specific pain qualities in CRPS patients with dystonia.

Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study.

Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement and cancer predisposition, caused by mutations in the A-T mutated (ATM) gene. To study genotype-phenotype correlations, we evaluated the clinical and laboratory data of 51 genetically proven A-T patients, and additionally measured ATM protein expression and kinase activity. Patients without ATM kinase activity showed the classical phenotype. The presence of ATM protein, correlated with slightly better immunological function. Residual kinase activity correlated with a milder and essentially different neurological phenotype, absence of telangiectasia, normal endocrine and pulmonary function, normal immunoglobulins, significantly lower X-ray hypersensitivity in lymphocytes, and extended lifespan. In these patients, cancer occurred later in life and generally consisted of solid instead of lymphoid malignancies. The genotypes of severely affected patients generally included truncating mutations resulting in total absence of ATM kinase activity, while patients with milder phenotypes harbored at least one missense or splice site mutation resulting in expression of ATM with some kinase activity. Overall, the phenotypic manifestations in A-T show a continuous spectrum from severe classical childhood-onset A-T to a relatively mild adult-onset disorder, depending on the presence of ATM protein and kinase activity. Each patient is left with a tremendously increased cancer risk.

Spreading of complex regional pain syndrome: not a random process.

Complex regional pain syndrome (CRPS) generally remains restricted to one limb but occasionally may spread to other limbs. Knowledge of the spreading pattern of CRPS may lead to hypotheses about underlying mechanisms but to date little is known about this process. The objective is to study patterns of spread of CRPS from a first to a second limb and the factors associated with this process. One hundred and eighty-five CRPS patients were retrospectively evaluated. Cox's proportional hazards model was used to evaluate factors that influenced spread of CRPS symptoms. Eighty-nine patients exhibited CRPS in multiple limbs. In 72 patients spread from a first to a second limb occurred showing a contralateral pattern in 49%, ipsilateral pattern in 30% and diagonal pattern in 14%. A trauma preceded the onset in the second limb in 37, 44 and 91%, respectively. The hazard of spread of CRPS increased with the number of limbs affected. Compared to patients with CRPS in one limb, patients with CRPS in multiple limbs were on average 7 years younger and more often had movement disorders. In patients with CRPS in multiple limbs, spontaneous spread of symptoms generally follows a contralateral or ipsilateral pattern whereas diagonal spread is rare and generally preceded by a new trauma. Spread is associated with a younger age at onset and a more severely affected phenotype. We argue that processes in the spinal cord as well as supraspinal changes are responsible for spontaneous spread in CRPS.

Thermal hypesthesia in patients with complex regional pain syndrome related dystonia.

The quantitative thermal test showed cold and warmth hypesthesia without increased heat pain sensitivity in the affected limbs of complex regional pain syndrome (CRPS) patients with tonic dystonia (n = 44) in comparison with healthy controls with a similar age and sex distribution (n = 35). The degrees of cold and warmth hypesthesia were strongly correlated. We conclude that dysfunction in small nerve fiber (i.e., C and Aδ) processing is present in patients with CRPS-related dystonia.

Spatiotemporal integration of sensory stimuli in complex regional pain syndrome and dystonia.

The aetiology of dystonia in complex regional pain syndrome (CRPS-I) is incompletely understood. In primary dystonia, somatosensory-evoked potentials (SSEP) after spatially or temporally separated stimulation revealed impaired central sensory integration. Information on somatosensory processing in dystonia in CRPS-I patients may provide better insight into the underlying pathophysiological mechanism. We studied SSEPs in 33 patients with CRPS-I and dystonia and 19 healthy controls. N9, N14, N20 and N35 amplitudes were recorded after paired stimulation of median and ulnar nerves ("spatial") and after stimulation of both nerves with single stimuli and with interstimulus intervals of 20 and 40 ms ("temporal" stimulation). Finally, both methods were integrated resulting in spatiotemporal stimulation. Statistical testing was performed using linear mixed model analysis of variance. SSEP amplitudes were significantly suppressed after spatial and temporal stimulation. No difference was observed between patients and healthy controls. Spatiotemporal stimulation did not show an additional suppressive effect in any group. Central sensory integration of proprioceptive afferent input is normal in patients with CPRS-related dystonia. Other mechanisms may underlie the development of dystonia in this disorder.

Psychological features of patients with complex regional pain syndrome type I related dystonia.

The objective of this study was to evaluate psychological features in severely affected patients with complex regional pain syndrome type I- (CRPS-I) related dystonia. Personality traits, psychopathology, dissociative experiences, the number of traumatic experiences, and quality of life were studied in 46 patients. Findings were compared with two historical psychiatric control groups [54 patients with conversion disorder (CD) and 50 patients with affective disorders (AD)] and normative population data. The CRPS-I patients showed elevated scores on the measures for somatoform dissociation, traumatic experiences, general psychopathology, and lower scores on quality of life compared with general population data, but had significantly lower total scores on the measures for personality traits, recent life events, and general psychopathology compared with the CD and AD patients. Rates of early traumatic experiences were comparable with the CD and AD patients, and the level of somatoform dissociation was comparable to the CD patients, but was elevated in comparison to the AD patients. Early traumatic experiences were reported in 87% of the CRPS-I patients and were found to be moderately related to somatoform dissociative experiences, indicating that early traumatic experiences might be a predisposing, although not a necessary factor for the development of CRPS-I-related dystonia. Although the psychological profile of the patients with CRPS-I-related dystonia shows some elevations, there does not seem to be a unique disturbed psychological profile on a group level.

Cerebral activation during motor imagery in complex regional pain syndrome type 1 with dystonia.

The pathogenesis of dystonia in Complex Regional Pain Syndrome type 1 (CRPS-1) is unclear. In primary dystonia, functional magnetic resonance imaging (fMRI) has revealed changes in cerebral networks during execution of movement. The aim of this study was to determine cerebral network function in CRPS-1 patients with dystonic postures. Cerebral processing related to both execution and imagining of hand movements in patients and controls was assessed with fMRI. Eight CRPS-1 patients with dystonic postures of the right upper extremity and 17 age-matched healthy controls were studied. Compared with controls, imaginary movement of the affected hand in patients showed reduced activation ipsilaterally in the premotor and adjacent prefrontal cortex, and in a cluster comprising frontal operculum, the anterior part of the insular cortex and the superior temporal gyrus. Contralaterally, reduced activation was seen in the inferior parietal and adjacent primary sensory cortex. There were no differences between patients and controls when they executed movements, nor when they imagined moving their unaffected hand. The altered cerebral activation pattern in patients with CRPS-1 linked dystonia most likely reflects an interface between pain-associated circuitry and higher order motor control, which points at a specific mechanistic pathophysiology of this type of dystonia.

Onset and progression of dystonia in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) may lead to movement disorders (MDs) in some patients. Reliable information on the nature, chronology and clinical determinants of MDs in CRPS patients is lacking but could provide better insight in to the underlying pathophysiological mechanism. We retrospectively evaluated the clinical and temporal characteristics of MDs in patients with CRPS. Cox's proportional hazards model was used to evaluate factors influencing the onset of MDs. One-hundred and eighty-five patients suffered CRPS in one or more extremities. MDs occurred in 121 patients, with dystonia (91%) being the most prevalent. Sixty-two percent of these patients displayed dystonia in multiple extremities. Patients with dystonia were on average 11 years younger and more often had CRPS in multiple extremities. The interval between the onset of CRPS and dystonia in the first affected extremity varied from less than 1 week in 26% of the patients to more than 1 year in 27%. The hazard of developing dystonia in subsequent extremities increased with the number of extremities affected by dystonia. We conclude that dystonia in CRPS shows highly variable onset latency and is associated with younger age at onset and increased risk of developing dystonia in other extremities. The delayed onset and progression of dystonia in CRPS may indicate the involvement of a different underlying mechanism, possibly associated with maladaptive neuroplasticity.