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Changes in ERP (P100 and N400) and root mean square (RMS) were obtained during a silent reading task in 28 patients with chronic post-stroke aphasia in a randomized, double-blind, placebo-controlled trial of both memantine and constraint-induced aphasia therapy (CIAT). Participants received memantine/placebo alone (weeks 0-16), followed by drug treatment combined with CIAT (weeks 16-18), and then memantine/placebo alone (weeks 18-20). ERP/RMS values (week 16) decreased more in the memantine group than in the placebo group. During CIAT application (weeks 16-18), improvements in aphasia severity and ERP/RMS values were amplified by memantine and changes remained stable thereafter (weeks 18-20). Changes in ERP/RMS occurred in left and right hemispheres and correlated with gains in language performance. No changes in ERP/RMS were found in a healthy group in two separated evaluations. Our results show that aphasia recovery induced by both memantine alone and in combination with CIAT is indexed by bilateral cortical potentials.

We report the rare case of a patient, JNR, with history of mixed handedness, developmental dyslexia, dysgraphia, and attentional deficits associated with a Klippel-Trenaunay syndrome and a small subcortical frontal lesion involving the left arcuate fasciculus. In adulthood, he suffered a large right perisylvian stroke and developed atypical conduction aphasia with deficits in input and output phonological processing and poor auditory-verbal short-term memory. Lexical-semantic processing for single words was intact, but he was unable to access meaning in sentence comprehension and repetition. Reading and writing deficits worsened after the stroke and he presented a combination of developmental and acquired dysgraphia and dyslexia with mixed lexical and phonological processing deficits. This case suggest that a small lesion sustained prenatally or early in life could induce a selective rightward shift of phonology sparing the standard left hemisphere lateralisation of lexical-semantic functions.

Although midbrain nuclei (substantia nigra, ventral tegmental area, and periaqueductal grey) are considered candidate loci of pathology in Tourette’s syndrome (TS), few imaging studies have examined midbrain structure. The objective of this study was to evaluate the presence of subtle structural abnormalities in the midbrain of patients with TS. High-field magnetic resonance imaging (MRI) (1.5- and 3-T) was used in 23 patients with TS and in 20 age- and sex-matched normal control subjects. Tics symptoms were rated using the Yale Global Tic Severity Scale and comorbid neuropsychiatric disorders were evaluated with standardised psychiatric rating scales. MRI scans revealed subtle structural abnormalities consistent with expanded perivascular spaces (EPVS) in the substantia nigra (compacta and reticulata) and neighbouring nuclei in 6 (26%) patients with TS, but in none of the normal control subjects (P = 0.045). Stereotyped movements were more frequent (P = 0.017) amongst TS patients with midbrain EPVS than in TS patients with normal MRI. Parkinsonism, posttraumatic stress disorder and autistic spectrum disorders exclusively occurred in TS patients with midbrain EPVS. There were no significant between-group differences in other comorbid neuropsychiatric disorders and in tics. Although EPVS are generally viewed as incidental findings, our results suggest that when EPVS are located in the midbrain they may be symptomatic. These abnormalities would reduce the actual number of neurons in specific midbrain nuclei (e.g., substantia nigra) and disrupt their connectivity with limbic, associative, and motor circuits.

Objective We conducted a randomized, double-blind, placebo-controlled, parallel-group study of both memantine and constraint-induced aphasia therapy (CIAT) on chronic poststroke aphasia followed by an open-label extension phase. Methods Patients were randomized to memantine (20mg/day) or placebo alone during 16 weeks, followed by combined drug treatment with CIAT (weeks 16–18), drug treatment alone (weeks 18–20), and washout (weeks 20–24), and finally, an open-label extension phase of memantine (weeks 24–48). After baseline evaluations, clinical assessments were done at two end points (weeks 16 and 18), and at weeks 20, 24, and 48. Outcome measures were changes in the Western Aphasia Battery-Aphasia Quotient and the Communicative Activity Log. Results Twenty-eight patients were included, and 27 completed both treatment phases. The memantine group showed significantly better improvement on Western Aphasia Battery-Aphasia Quotient compared with the placebo group while the drug was taken (week 16, p = 0.002; week 18, p = 0.0001; week 20, p = 0.005) and at the washout assessment (p = 0.041). A significant increase in Communicative Activity Log was found in favor of memantine-CIAT relative to placebo-CIAT (week 18, p = 0.040). CIAT treatment led to significant improvement in both groups (p = 0.001), which was even greater under additional memantine treatment (p = 0.038). Beneficial effects of memantine were maintained in the long-term follow-up evaluation, and patients who switched to memantine from placebo experienced a benefit (p = 0.02). Interpretation Both memantine and CIAT alone improved aphasia severity, but best outcomes were achieved combining memantine with CIAT. Beneficial effects of memantine and CIAT persisted on long-term follow-up. Ann Neurol 2009;65:577–585