Autistic-like findings associated with a urea cycle disorder in a 4-year-old girl

A 4-year-old girl presented at our clinic with autistic-like symptoms, aggressivity and occasional hyperactivity. She had no history of neurologic or physical symptoms. Her condition was diagnosed as pervasive developmental disorder not otherwise specified, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). She received pharmacologic (thioridazine), educational and speech therapy. During this process, a urea cycle disorder was also identified, namely, ornithine transcarbamylase deficiency and arginase deficiency, because of the high level of ammonia in the patient's bloodstream, the high level of organic acids in the 24-hour urine collection and the constant presence of slow multifocal epileptic discharges on the electroencephalograms. The patient's protein intake was restricted, and she was treated with sodium benzoate and arginine. After 1 year of treatment, the autistic-like findings and hyperactivity were no longer apparent.     

High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: response to treatment with levetiracetam

OBJECTIVE: Abnormalities in brain gamma-aminobutyric acid (GABA) and glutamate may be relevant to the underlying pathophysiology of anxiety disorders including social anxiety disorder (SAD). METHODS: We used proton magnetic resonance spectroscopy (pMRS) to examine whole brain and regional GABA, glutamate and glutamine in patients (N=10) with SAD at baseline compared to a matched group of healthy controls (HC), and changes following 8 weeks of pharmacotherapy with levetiracetam. RESULTS: For SAD subjects, there were significantly higher whole brain levels of glutamate and glutamine, though no significant differences in GABA. In the thalamus, glutamine was higher and GABA lower for SAD subjects. There was a significant reduction in thalamic glutamine with levetiracetam treatment. CONCLUSION: Our findings provide preliminary support for impaired GABAergic and overactive glutamatergic function in social anxiety disorder and the potential relevance of changes in these systems for the anxiolytic response to levetiracetam.     

Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study

There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD—the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)—and one ‘control'' region—the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal ‘control'' region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate–glutamine levels are not explained by use of stimulant medication.     

Extensive cortical magnetic resonance signal change in proximal urea cycle disorder

The authors report a 3-year 8-month-old girl presenting with episodic hyperammonemic encephalopathy probably due to a proximal urea cycle disorder. The magnetic resonance imaging (MRI) of the brain performed during the third episode revealed extensive and diffuse cerebral cortical signal changes with sparing of occipital cortex. It is believed that intracerebral accumulation of glutamine mainly in astrocytes is the major cause of the encephalopathy. This results in astrocyte swelling, brain edema, intracranial hypertension, and cerebral hypoperfusion.     

Brain imaging in a patient with hemimicropsia

Hemimicropsia is an isolated misperception of the size of objects in one hemifield (objects appear smaller) which is, as a phenomenon of central origin, very infrequently reported in literature. We present a case of hemimicropsia as a selective deficit of size and distance perception in the left hemifield without hemianopsia caused by a cavernous angioma with hemorrhage in the right occipitotemporal area. The symptom occurred only intermittently and was considered the consequence of a local irritation by the hemorrhage. Imaging data including a volume-rendering MR data set of the patient's brain were transformed to the 3-D stereotactic grid system by Talairach and warped to a novel digital 3-D brain atlas. Imaging analysis included functional MRI (fMRI) to analyse the patient's visual cortex areas (mainly V5) in relation to the localization of the hemangioma to establish physiological landmarks with respect to visual stimulation. The lesion was localized in the peripheral visual association cortex, Brodmann area (BA) 19, adjacent to BA 37, both of which are part of the occipitotemporal visual pathway. Additional psychophysical measurements revealed an elevated threshold for perceiving coherent motion, which we relate to a partial loss of function in V5, a region adjacent to the cavernoma. In our study, we localized for the first time a cerebral lesion causing micropsia by digital mapping in Talairach space using a 3-D brain atlas and topologically related it to fMRI data for visual motion. The localization of the brain lesion affecting BA 19 and the occipitotemporal visual pathway is discussed with respect to experimental and case report findings about the neural basis of object size perception.     

颅脑损伤合并非酮性高血糖高渗性昏迷

目的 探讨颅脑损伤并发非酮性高血糖高渗性昏迷病人的诊断、治疗及预后。方法 对1997年7月～2002年1月期间收治的17例中、重型颅脑损伤合并非酮性高血糖高渗性昏迷的病人进行回顾性分析。结果 17例颅脑损伤合并非酮性高血糖高渗性昏迷的病人，除1例之外，其余均在静滴胰岛素及胃内注水治疗后2d内，高血糖、高血渗得到控制。17例非酮性高血糖高渗性昏迷病例占同期中、重型颅脑损伤病人的1．76％。死亡3例，死亡率17．6％。结论 对非酮性高血糖高渗性昏迷，静滴胰岛素极其有效，救治的关键是及早发现行采取有效的治疗措施。治疗中连续性监测血糖、血清渗透压、电解质、严密的病情监护，及时有效调整胰岛素用量至关重要。     

Tongue tremor in a patient with coma after electrical injury.

We report on the case of a patient with transient tongue tremor and coma after electrical injury, probably due to a reversible brainstem dysfunction. We then reviewed the differential diagnosis of abnormal involuntary movements of the tongue as well as movement disorders related to electrocution.     

Structural MRI and MRS abnormalities in bipolar disorder

Soares JC. Structural MRI and MRS abnormalities in bipolar disorder. Bipolar Disord 2002: 4(Suppl. 1): 87. © Blackwell Munksgaard, 2002     

Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers

OBJECTIVE: This in vivo (1)H magnetic resonance spectroscopy study examined levels of glutamate, glutamine, and N-acetylaspartate in patients experiencing their first episode of schizophrenia. METHOD: Localized in vivo (1)H spectra were acquired at 4.0 T from the left anterior cingulate and thalamus of 21 never-treated patients with schizophrenia and 21 comparable healthy volunteers. RESULTS: The level of glutamine was significantly higher in the left anterior cingulate cortex and thalamus of the patients with schizophrenia than in the healthy subjects. No differences were found between groups in the levels of other metabolites in the anterior cingulate or thalamus. CONCLUSIONS: Higher than normal glutamine levels in the left anterior cingulate and thalamus provide in vivo evidence of greater than normal glutamatergic activity proposed by glutamatergic models of schizophrenia. In contrast to other studies in chronically ill patients, no differences were seen in the levels of N-acetylaspartate in either location, suggesting that the findings in patients with chronic schizophrenia may be related to the effect of medication or the progression of the illness.     

Medication-induced somnambulism in a patient with schizoaffective disorder

A 39-year-old man with schizoaffective disorder experienced somnambulism only when taking a combination of lithium carbonate, chlorpromazine, triazolam, and benztropine. This was confirmed in the sleep laboratory. The sleepwalking occurred during Stage 2 sleep; the sleep record showed a marked paucity of REM sleep. The patient's brother had had one episode of somnambulism, also following exposure to a substance affecting the CNS. A role for CNS-active medications in triggering some pathologic sleep phenomena in predisposed individuals is hypothesized. Medications with central anticholinergic activity may be particularly important.     

Cholestatic jaundice induced by duloxetine in a patient with major depressive disorder

Duloxetine is a balanced and potent serotonin and noradrenaline reuptake inhibitor (SNRI) and has adverse effects that are commonly associated with such drugs, including nausea, dry mouth, constipation, insomnia, and dizziness. Recently, duloxetine-induced liver injury has also been observed in patients with preexisting liver disease or chronic alcohol use. We investigated the effects of duloxetine in a healthy young adult with major depressive disorder (MDD) but no risk factors, and found that his total bilirubin level increased to 3.3 mg/dL and he developed jaundice after 5 months of duloxetine treatment. Discontinuation of duloxetine treatment saw his total bilirubin level decrease to 1.8 mg/dL. Thus, the administration of duloxetine might induce liver injury in a patient with MDD. However, the limitations of this single case report must be acknowledged. Although the cause of hepatic dysfunction in this case remains to be elucidated, clinicians should monitor liver function carefully after duloxetine treatment. Further investigations with a larger sample are needed.