Locked-in syndrome after central pontine myelinolysis, an outstanding outcome of two patients.

OBJECTIVE: Central pontine myelinolysis (CPM) is a rare demyelinating disease that affects the pons and which can cause extreme disabilities such as locked-in syndrome (LIS) in the initial phase. The aim of the study was to describe the evolution over a 12-month period of two patients with CPM causing an initial LIS. METHOD: We retrospectively report the unexpected clinical outcome of these two patients in relation with the anatomical damages documented by brain MRI, associated with diffusion tensor imaging and reconstruction of corticospinal tracts in tractography. The following clinical parameters systematically assessed at 3, 6, 9, and 12 months: muscle testing on 12 key muscles (Medical Research Council), prehension metrics (box and block test and purdue pegboard), and independence for acts of daily living (functional independence measure). RESULTS: Both patients showed a progressive recovery beginning between 2 and 3 months after the onset of symptoms, leading to almost complete autonomy at 12 months (FIM > 110), with motor strength greater than 4/5 in all joint segments (MRC > 50/60). On brain MRI with tractography, CST appeared partially preserved at pons level. INTERPRETATION: The possibility of a near-complete functional recovery at 12 months is important to consider given the ethical issues at stake and the discussions about limiting care that may take place initially. It seems to be the consequence of reversible myelin damage combined with partially preserved neurons. Development of collateral pathways or resolution of conduction block may explain this recovery. MRI comprising DTI and tractography could play a key role in the prognosis of motor recovery.

Adding methylphenidate to prism-adaptation improves outcome in neglect patients. A randomized clinical trial.

Spatial neglect is one of the main predictors of poor functional recovery after stroke. Many therapeutic interventions have been developed to alleviate this condition, but to date the evidence of their effectiveness is still scarce. OBJECTIVE: The purpose of this study was to test whether combining prism adaptation (PA) and methylphenidate (MP) could enhance the recovery of neglect patients at a functional level. METHODS: RITAPRISM is a multicentre, randomized, double-blind, placebo-controlled study comparing PA plus placebo (control) versus PA plus MP. 24 patients were prospectively enrolled (10 in the placebo group and 14 in the MP group). RESULTS: The main result is a long-term functional improvement (on the functional independence measure (FIM) and on Bergego's scale) induced by MP combined with PA. No serious adverse event occurred. CONCLUSIONS: The long-term benefit on activities of daily living (ADL) obtained in this randomized controlled trial set this intervention apart from previous attempts and supports with a high level of evidence the value of combining PA and MP in order to improve the autonomy of neglect patients. Further studies will be needed to clarify the mechanism of this improvement. Although not specifically assessed at this stage, a part of the improvement in ADL might be related to the collateral effect of MP on mood, executive functions or fatigue, and/or the combined effect of PA and MP on motor intentional bias of neglect patients. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that adding MP to PA improves the functional outcome of neglect patients. WHO TRIAL REGISTRATION ID: EUCTR2008-000325-20-FR.

Degeneration of the Arnold's prefrontopontocerebellar tract in a case of locked-in syndrome over a 23-year period.

A 52-year-old woman has been under observation for a complete locked-in syndrome of vascular origin, since 1984. Her cognitive functions today are still normal. When first diagnosed, a CT-scan was made and 23 years later performed, a cerebral MRI was performed. A focal, bilateral and symmetric atrophy of the dorsomedial prefrontal gyri was clearly shown, contrasting with the non-atrophy of the precentral gyri (motor area), others prefrontal areas, frontopolar gyri and temporal cortices. Degeneration of the corticopontine projection, the first step in the corticopontocerebellar circuit, could explain this selective atrophy. This unique observation leads to the precise in vivo anatomical location of the Arnold tract.

Altered awareness of voluntary action after damage to the parietal cortex.

A central question in the study of human behavior is the origin of willed action. EEG recordings of surface brain activity from human subjects performing a self-initiated movement show that the subjective experience of wanting to move follows, rather than precedes, the 'readiness potential'--an electrophysiological mark of motor preparation. This raises the issue of how conscious experience of willed action is generated. Here we show that patients with parietal lesions can report when they started moving, but not when they first became aware of their intention to move. This stands in contrast with the performance of cerebellar patients who behaved as normal subjects. We thus propose that when a movement is planned, activity in the parietal cortex, as part of a cortico-cortical sensorimotor processing loop, generates a predictive internal model of the upcoming movement. This model might form the neural correlate of motor awareness.