Functional consequences of mutations in the human alpha1A calcium channel subunit linked to familial hemiplegic migraine.
Mutations in alpha1A, the pore-forming subunit of P/Q-type calcium channels, are linked to several human diseases, including familial hemiplegic migraine (FHM). We introduced the four missense mutations linked to FHM into human alpha1A-2 subunits and investigated their functional consequences after expression in human embryonic kidney 293 cells. By combining single-channel and whole-cell patch-clamp recordings, we show that all four mutations affect both the biophysical properties and the density of functional channels. Mutation R192Q in the S4 segment of domain I increased the density of functional P/Q-type channels and their open probability. Mutation T666M in the pore loop of domain II decreased both the density of functional channels and their unitary conductance (from 20 to 11 pS). Mutations V714A and I1815L in the S6 segments of domains II and IV shifted the voltage range of activation toward more negative voltages, increased both the open probability and the rate of recovery from inactivation, and decreased the density of functional channels. Mutation V714A decreased the single-channel conductance to 16 pS. Strikingly, the reduction in single-channel conductance induced by mutations T666M and V714A was not observed in some patches or periods of activity, suggesting that the abnormal channel may switch on and off, perhaps depending on some unknown factor. Our data show that the FHM mutations can lead to both gain- and loss-of-function of human P/Q-type calcium channels. (+info)
A clinical guide to assess the role of lower limb extensor overactivity in hemiplegic gait disorders.
BACKGROUND AND PURPOSE: The aim of this study was to assess the role of knee and ankle extensor overactivity in the hemiplegic gait observed in stroke victims and to propose a clinical guide for selecting patients before treatment of a supposed disabling spasticity. METHODS: A standardized physical examination procedure was performed in 135 consecutive stroke patients. All patients were able to walk without human assistance. The period after stroke ranged from 3 to 24 months (mean, 11.5+/-7.25 months). Spasticity was evaluated with the stroke victim in sitting position and during walking. Overactivity of the quadriceps was considered disabling when inducing inability to flex the knee during the swing phase despite adequate control of knee flexion in sitting and standing positions; overactivity of the triceps surae was considered to be disabling when heel strike was not possible despite good control of the ankle flexion in sitting position; triceps retraction was also considered. RESULTS: Disabling overactivity was observed in 56 (41.5%) patients: 11 times for the quadriceps femoris, 21 times for the triceps surae, and 21 times for both muscles. It was considered to be the main disorder impairing gait among only 16 (12%) patients: 9 for the quadriceps alone, 3 for the triceps alone, and 4 for both. Sitting spasticity of the lower limb was not predictive of disabling overactivity during walking. CONCLUSIONS: Extensor muscle overactivity is one of the components of gait disorders in stroke patients. The difficulty in assessing spasticity and its real causal effect in gait disturbances are discussed. A clinical guide is proposed. (+info)
Activation of selected trunk muscles during symmetric functional activities in poststroke hemiparetic and hemiplegic patients.
OBJECTIVE: To compare the EMG activity between the recti abdominii muscles and between the lumbar erector spinae muscles in hemiparetic and hemiplegic patients during functional symmetric trunk movements and to compare patients' EMG activity profiles with those of healthy controls. METHODS: EMG activity from the selected muscles was recorded during three symmetric and time controlled trunk exercises. Data analysis was based on values of cross correlations and of ratios between EMG activity of the bilateral corresponding muscles. RESULTS: In all groups, the highest cross correlations were obtained for both muscles when the muscles acted as prime movers. For the recti abdominii muscles, these values in the patients were comparable with those of the healthy subjects, whereas for the extensor muscles, the highest synchronous activity was displayed in healthy subjects and the lowest in hemiplegic patients. Laterality differences in the amount of EMG activity of the recti abdominii muscles were not biased towards one side. For the extensor muscles, in the controls, the activation levels were higher in the left erector spinae muscle than in the right one in two of the three exercises. Similarly, in the extensor muscles of the hemiparetic patients, activity on the paretic side was higher than on the non-paretic side in two exercises. CONCLUSIONS: In patients with a supratentorial poststroke hemiparesis or hemiplegia, bilateral corresponding axial trunk muscles co-contract during symmetric trunk activities. Synchronous activation is at its highest level during voluntary dynamic tasks and is greater in the recti abdominii than in the erector spinae muscles. For both muscles, EMG activation levels on the paretic side were not lower than on the non-paretic side. Thus, the assertion that the muscles on the paretic side are activated to a lesser extent than their counterparts on the non-paretic side during symmetric trunk movements was not confirmed. (+info)
Global aphasia without hemiparesis: language profiles and lesion distribution.
OBJECTIVES: Global aphasia without hemiparesis (GAWH) is an uncommon stroke syndrome involving receptive and expressive language impairment, without the hemiparesis typically manifested by patients with global aphasia after large left perisylvian lesions. A few cases of GAWH have been reported with conflicting conclusions regarding pathogenesis, lesion localisation, and recovery. The current study was conducted to attempt to clarify these issues. METHODS: Ten cases of GAWH were prospectively studied with language profiles and lesion analysis; five patients had multiple lesions, four patients had a single lesion, and one had a subarachnoid haemorrhage. Eight patients met criteria for cardioembolic ischaemic stroke. RESULTS: Cluster analysis based on acute language profiles disclosed three subtypes of patients with GAWH; these clusters persisted on follow up language assessment. Each cluster evolved into a different aphasia subtype: persistent GAWH, Wernicke's aphasia, or transcortical motor aphasia (TCM). Composite lesion analysis showed that persistent GAWH was related to lesioning of the left superior temporal gyrus. Patients with acute GAWH who evolved into TCM type aphasia had common lesioning of the left inferior frontal gyrus and adjacent subcortical white matter. Patients with acute GAWH who evolved into Wernicke's type aphasia were characterised by lesioning of the left precentral and postcentral gyri. Recovery of language was poor in all but one patient. CONCLUSIONS: Although patients with acute GAWH are similar on neurological examination, they are heterogeneous with respect to early aphasia profile, language recovery, and lesion profile. (+info)
Sparing effect of hemiplegia on tophaceous gout.
The sparing effect of hemiplegia on the development of tophaceous gout is described. The useless upper limb had no tophaceous deposits and the partially paralysed lower limb had only limited urate deposits. Disuse was presumably the major contributor to the limited deposition of urates on the paralysed side. (+info)
Surgical treatment of internal carotid artery anterior wall aneurysm with extravasation during angiography--case report.
A 54-year-old female presented subarachnoid hemorrhage from an aneurysm arising from the anterior (dorsal) wall of the internal carotid artery (ICA). During four-vessel angiography, an extravasated saccular pooling of contrast medium emerged in the suprasellar area unrelated to any arterial branch. The saccular pooling was visualized in the arterial phase and cleared in the venophase during every contrast medium injection. We suspected that the extravasated pooling was surrounded by hard clot but communicated with the artery. Direct surgery was performed but major premature bleeding occurred during the microsurgical procedure. After temporary clipping, an opening of the anterior (dorsal) wall of the ICA was found without apparent aneurysm wall. The vessel wall was sutured with nylon thread. The total occlusion time of the ICA was about 50 minutes. Follow-up angiography demonstrated good patency of the ICA. About 2 years after the operation, the patient was able to walk with a stick and to communicate freely through speech, although left hemiparesis and left homonymous hemianopsia persisted. The outcome suggests our treatment strategy was not optimal, but suture of the ICA wall is one of the therapeutic choices when premature rupture occurs in the operation. (+info)
Impaired modulation of quadriceps tendon jerk reflex during spastic gait: differences between spinal and cerebral lesions.
In healthy subjects, functionally appropriate modulation of short latency leg muscle reflexes occurs during gait. This modulation has been ascribed, in part, to changes in presynaptic inhibition of Ia afferents. The changes in modulation of quadriceps tendon jerk reflexes during gait of healthy subjects were compared with those of hemi- or paraparetic spastic patients. The spasticity was due to unilateral cerebral infarction or traumatic spinal cord injury, respectively. The modulation of the quadriceps femoris tendon jerk reflex at 16 phases of the step cycle was studied. The reflex responses obtained during treadmill walking were compared with control values obtained during gait-mimicking standing postures with corresponding levels of voluntary muscle contraction and knee angles. In healthy subjects the size of the reflexes was profoundly modulated and was generally depressed throughout the step cycle. In patients with spinal lesion the reflex depression during gait was almost removed and was associated with weak or no modulation during the step cycle. In patients with cerebral lesion there was less depression of the reflex size associated with a reduced reflex modulation on the affected side compared with healthy subjects. On the 'unaffected' side of these patients reflex modulation was similar to that of healthy subjects, but the reflex size during gait was not significantly different from standing control values. These observations suggest that the mechanisms responsible for the depression of reflex size and the modulation normally seen during gait in healthy subjects are impaired to different extents in spasticity of spinal or cerebral origin, possibly due to the unilateral preservation of fibre tracts in hemiparesis. (+info)
Aphasic disorder in patients with closed head injury.
Quantitative assessment of 50 patients with closed head injury disclosed that anomic errors and word finding difficulty were prominent sequelae as nearly half of the series had defective scores on tests of naming and/or word association. Aphasic disturbance was associated with severity of brain injury as reflected by prolonged coma and injury of the brain stem. (+info)