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1.
Pediatr Blood Cancer ; 65(12): e27373, 2018 12.
Article in English | MEDLINE | ID: mdl-30084242
2.
Exp Neurol ; 289: 96-102, 2017 03.
Article in English | MEDLINE | ID: mdl-28038988

ABSTRACT

Neural stem cells (NSCs) are being investigated as a possible treatment for amyotrophic lateral sclerosis (ALS) through intraspinal transplantation, but no longitudinal imaging studies exist that describe the survival of engrafted cells over time. Allogeneic firefly luciferase-expressing murine NSCs (Luc+-NSCs) were transplanted bilaterally (100,000 cells/2µl) into the cervical spinal cord (C5) parenchyma of pre-symptomatic (63day-old) SOD1G93A ALS mice (n=14) and wild-type age-matched littermates (n=14). Six control SOD1G93A ALS mice were injected with saline. Mice were immunosuppressed using a combination of tacrolimus+sirolimus (1mg/kg each, i.p.) daily. Compared to saline-injected SOD1G93A ALS control mice, a transient improvement (p<0.05) in motor performance (rotarod test) was observed after NSC transplantation only at the early disease stage (weeks 2 and 3 post-transplantation). Compared to day one post-transplantation, there was a significant decline in bioluminescent imaging (BLI) signal in SOD1G93A ALS mice at the time of disease onset (71.7±17.9% at 4weeks post-transplantation, p<0.05), with a complete loss of BLI signal at endpoint (120day-old mice). In contrast, BLI signal intensity was observed in wild-type littermates throughout the entire study period, with only a 41.4±8.7% decline at the endpoint. In SOD1G93A ALS mice, poor cell survival was accompanied by accumulation of mature macrophages and the presence of astrogliosis and microgliosis. We conclude that the disease progression adversely affects the survival of engrafted murine Luc+-NSCs in SOD1G93A ALS mice as a result of the hostile ALS spinal cord microenvironment, further emphasizing the challenges that face successful cell therapy of ALS.


Subject(s)
Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/surgery , Neural Stem Cells/transplantation , Amyotrophic Lateral Sclerosis/genetics , Animals , Cell Survival , Disease Models, Animal , Disease Progression , Embryo, Mammalian , Follow-Up Studies , Immunosuppressive Agents/pharmacology , Luciferases/metabolism , Male , Mice , Mice, Transgenic , Motor Activity/drug effects , Motor Activity/physiology , Nerve Tissue Proteins/metabolism , Psychomotor Disorders/etiology , Psychomotor Disorders/surgery , Sirolimus/pharmacology , Spinal Cord/diagnostic imaging , Spinal Cord/surgery , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Tacrolimus/pharmacology , Transplantation, Homologous
3.
Epilepsia ; 55(5): 683-689, 2014 May.
Article in English | MEDLINE | ID: mdl-24621276

ABSTRACT

OBJECTIVE: Some patients with Sturge-Weber syndrome (SWS) need epilepsy surgery for adequate seizure control and prevention of psychomotor deterioration. The majority of patients with SWS have leptomeningeal angioma located over the temporal, parietal, and occipital lobes. We applied posterior quadrant disconnection surgery for this type of SWS with intractable seizure. We evaluated the efficacy of this procedure in seizure control and psychomotor development. METHODS: Ten patients who were surgically treated using the posterior quadrantectomy (PQT) were enrolled in this study. Surgical outcome was analyzed as seizure-free or not at 2 years after surgery. Psychomotor development was evaluated by the scores of mental developmental index (MDI) and psychomotor developmental index (PDI) in the Bayley Scales of Infant Development II preoperatively, and at 6 and 12 months after the PQT. RESULTS: Eight of 10 patients were seizure-free. Patients without complete elimination of the angiomatous areas had residual seizures. Average MDI and PDI scores before the surgery were 64.8 and 71.6, respectively. Scores of MDI at 6 and 12 months after the PQT in seizure-free patients were 80.5 and 84.5, respectively (p < 0.01). PDI scores at these postoperative intervals were 87.3 and 86.4, respectively (p < 0.05). Patients with residual seizures did not improve in either MDI or PDI. SIGNIFICANCE: The PQT achieved good seizure control and improved psychomotor development in patients with SWS. The complete deafferentation of angiomatous areas is required for seizure-free results and psychomotor developmental improvement.


Subject(s)
Craniotomy/methods , Epilepsy, Tonic-Clonic/surgery , Neural Pathways/surgery , Neuronavigation/methods , Occipital Lobe/surgery , Parietal Lobe/surgery , Sturge-Weber Syndrome/surgery , Temporal Lobe/surgery , Corpus Callosum/surgery , Epilepsy, Tonic-Clonic/diagnosis , Hemangioma/diagnosis , Hemangioma/surgery , Humans , Image Enhancement , Magnetic Resonance Imaging , Meningeal Neoplasms/surgery , Psychomotor Disorders/diagnosis , Psychomotor Disorders/surgery , Sturge-Weber Syndrome/diagnosis
6.
Dev Med Child Neurol ; 49(5): 385-9, 2007 May.
Article in English | MEDLINE | ID: mdl-17489815

ABSTRACT

The aim of this review was to examine the literature on the effects of surgery of the spastic hand in children with cerebral palsy on functional outcome and muscle coordination. We performed a search of the relevant literature in Medline, Embase, and Biological Abstracts from 1966 to June 2006. The search resulted in eight studies on the effect of surgery on functional outcome and three studies on the effect of surgery on muscle coordination. Heterogeneity in outcome measures precluded meta-analysis. The studies revealed that -- at the level of impairment -- surgery has a positive effect on supination and dorsiflexion of the wrist. At the level of function, surgery might improve grip strategy and induce an increase of the repertoire of grips and spontaneous use of the hand. The evidence for the functional effects is, however, limited. Whether the possibly improved function is mediated by alterations in muscle coordination patterns remains unclear. The muscle coordination studies provided inconclusive results. We concluded that surgery improves the position of the hand and there are indications that it might improve hand function. Future research should address the question: does surgery improve hand function and, if so, is this due solely to a better hand position or does change in muscle coordination play an additional role?


Subject(s)
Cerebral Palsy/surgery , Functional Laterality/physiology , Hand/surgery , Adolescent , Adult , Cerebral Palsy/physiopathology , Child , Child, Preschool , Hand Strength/physiology , Humans , Infant , Motor Skills/physiology , Muscle Spasticity/physiopathology , Muscle Spasticity/surgery , Psychomotor Disorders/physiopathology , Psychomotor Disorders/surgery , Treatment Outcome
7.
Dev Med Child Neurol ; 49(4): 289-93, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17376140

ABSTRACT

Chiari type II malformation (CII) is a congenital anomaly of the cerebellum and brainstem, both important structures for processing smooth ocular pursuit. CII is associated with myelomeningocele and hydrocephalus. We investigated the effects of CII on smooth pursuit (SP) eye movements, and determined the effects of spinal lesion level, number of shunt revisions, nystagmus, and brain dysmorphology on SP. SP was recorded using an infrared eye tracker in 21 participants with CII (11 males, 10 females; age range 8-19y, mean 14y 3mo [SD 3y 2mo]). Thirty-eight healthy children (21 males, 17 females) constituted the comparison group. Participants followed a visual target moving sinusoidally at +/- 10 degrees amplitude, horizontally and vertically at 0.25 or 0.5Hz. SP gains, the ratio of eye to target velocities, were abnormal in the CII group with nystagmus (n= 8). The number of shunt revisions (range 0-10), brain dysmorphology, or spinal lesion level (n= 15 for lower and n= 6 for upper spinal lesion level) did not correlate with SP gains. SP is impaired in children with CII and nystagmus. Abnormal pursuit might be related to the CII dysgenesis or to effects of hydrocephalus. The lack of effect of shunt revisions and abnormal tracking in participants with nystagmus provide evidence that it is related primarily to the cerebellar and brainstem malformation.


Subject(s)
Arnold-Chiari Malformation/physiopathology , Pursuit, Smooth/physiology , Adolescent , Arnold-Chiari Malformation/diagnosis , Arnold-Chiari Malformation/surgery , Brain Stem/abnormalities , Brain Stem/physiopathology , Cerebellum/abnormalities , Cerebellum/physiopathology , Cerebrospinal Fluid Shunts , Child , Female , Humans , Hydrocephalus/diagnosis , Hydrocephalus/physiopathology , Hydrocephalus/surgery , Male , Meningomyelocele/diagnosis , Meningomyelocele/physiopathology , Meningomyelocele/surgery , Neurologic Examination , Nystagmus, Congenital/diagnosis , Nystagmus, Congenital/physiopathology , Postoperative Complications/diagnosis , Postoperative Complications/physiopathology , Postoperative Complications/surgery , Psychomotor Disorders/diagnosis , Psychomotor Disorders/physiopathology , Psychomotor Disorders/surgery , Reaction Time/physiology , Reoperation , Risk Factors
8.
Nervenarzt ; 75(7): 691-3, 2004 Jul.
Article in German | MEDLINE | ID: mdl-15300326

ABSTRACT

A patient showing "prodromal symptoms" of suspected psychosis was referred to our clinic specialized in early recognition of schizophrenia where an MRI brain scan showed a chronic subdural hemorrhage. Based on this case, it will be shown that organic brain disease, in addition to incipient schizophrenia, needs to be considered in patients with marked personality changes, social withdrawal, aggressiveness, and suspiciousness. Diagnosis of the first episode and prodromal stage of schizophrenia should include-apart from the case history as well as the psychopathological and physiological findings-certain obligatory medical examinations (EEG, cCT, or MRI) in order to identify possible organic causes and avoid misdiagnoses.


Subject(s)
Hematoma, Subdural, Chronic/diagnosis , Schizophrenia/diagnosis , Schizophrenic Psychology , Schizotypal Personality Disorder/diagnosis , Adult , Brain/pathology , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Cognition Disorders/surgery , Diagnosis, Differential , Early Diagnosis , Follow-Up Studies , Hematoma, Subdural, Chronic/psychology , Hematoma, Subdural, Chronic/surgery , Humans , Magnetic Resonance Imaging , Male , Postoperative Complications/diagnosis , Postoperative Complications/psychology , Psychomotor Disorders/diagnosis , Psychomotor Disorders/psychology , Psychomotor Disorders/surgery , Schizophrenia/surgery , Schizotypal Personality Disorder/psychology , Schizotypal Personality Disorder/surgery
9.
Padiatr Padol ; 25(5): 363-70, 1990.
Article in German | MEDLINE | ID: mdl-2287515

ABSTRACT

In cerebral palsy orthopedic surgery can avoid deformity, existing deformities can be corrected, muscle imbalance can balanced and painful conditions--such as early osteoarthritis in hip dislocation--can be diminished. A tremendous functional improvement is not to be expected. In order to achieve good results the correct diagnosis is important, the natural course of the disease must be known. A team approach that includes the pediatric neurologist, physical therapist and the orthopedic surgeon is a must. The goals of therapy have to be discussed with the patient and his/her parents. If possible electromyography and gait analysis should be done but exact clinical evaluation is most important. The interactions between different groups of muscles must be known. It is important to differentiate primary and secondary, dynamic and fixed deformities. Orthopedic surgery can make life easier for a person with cerebral palsy, but cerebral palsy itself can never be over come.


Subject(s)
Cerebral Palsy/surgery , Hemiplegia/surgery , Psychomotor Disorders/surgery , Ankle Joint/surgery , Child , Hip Joint/surgery , Humans , Knee Joint/surgery
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