Case report: Early-onset parkinsonism among the neurological features in children with PHACTR1 variants.

PACHTR1 is expressed in cardiovascular and neurological tissues. In the brain, it has a role in pre- and post-natal maturation. Previously reported PHACTR1-mutated patients showed early-onset epilepsy and intellectual disability. We describe two unreported cases with de novo pathogenic variants in PHACTR1 and their clinical pictures, compared with those of cases already reported in the literature. In line with previous reports, the two patients presented early-onset developmental and epileptic encephalopathy. In addition, one patient developed a speech disorder and a progressive movement disorder characterized by hypertonus, hypo-bradykinesia, hypomimia, ataxic gait, and retropulsion. She was treated with levodopa without any clinical improvement. Pathogenic variants in PHACTR1 may result in a cardiological or neurological phenotype. Severe developmental delay, intellectual disability, and early-onset developmental and epileptic encephalopathy are the main features of PHACTR1-mutated patients with neurological involvement. Movement and speech disorders have never previously been described and could be new features of the neurological phenotype.

Intrathecal baclofen and motor function in cerebral palsy.

AIM: The aim of this retrospective analysis was to determine the impact of intrathecal baclofen (ITB) therapy on motor function in patients with cerebral palsy (CP). METHOD: We studied 37 patients (18 males, 19 females) with CP treated with ITB (mean age at implant 13 y 7 mo, SD 7 y). Eighteen patients were affected by spastic diplegia, 12 by spastic quadriplegia, six by dystonic quadriplegia, and one by hemidystonia. Nine participants were in Gross Motor Function Classification System (GMFCS) level II, 13 in level III, seven in level IV, and eight in level V. Motor function was assessed by the Gross Motor Function Measure (GMFM) before the treatment and 12 months after the implant. RESULTS: The collected data showed an increase in the total median GMFM score in the overall population (p<0.001) and in every GMFM dimension (p<0.05) except for dimension D (standing). The analysis by degree of impairment revealed that patients with severe impairment and those with mild to moderate impairment improved the total median GMFM score (p<0.001 and p<0.05 respectively). Analysis by age showed that the best improvements in GMFM scores were reached by patients younger than 18 years old (p<0.05). Spasticity and dystonia, assessed by means of the Ashworth and Barry-Albright Dystonia scales, significantly decreased 12 months after the implant (p<0.001 and p<0.05 respectively). Finally, a subjective questionnaire administered to patients/caregivers revealed an overall improvement in participants' functional abilities. INTERPRETATION: The results suggest that ITB therapy is an effective treatment for managing spasticity and dystonia, and for improving motor function in children with CP.

Forced-use, without therapy, in children with hemiplegia: preliminary study of a new approach for the upper limb.

BACKGROUND: Forced use (FU) is an emerging treatment for children with hemiplegic cerebral palsy (CP). It involves constraining the unaffected arm and no additional treatment of the affected arm. Our study examined a new approach to FU in children with hemiplegic CP: that is, restraint of the unaffected limb and no rehabilitation. METHODS: Ten children with hemiplegic CP aged between 5 and 9 years were compared with 10 control children (aged between 5 and 8 y). All participants were classified as MACS level II.The FU group wore a fixed cast, on the unaffected arm for 21 consecutive days, and, such as the control group, did not receive any physical therapy.All participants were assessed by the Melbourne Assessment of Unilateral Upper Limb Function and the Shriners Hospital Upper Extremity Evaluation. RESULTS: A statistically significant increase in both the functional scales was already apparent after cast removal and was maintained during follow-ups. The total Melbourne Assessment of Unilateral Upper Limb Function percentage score increased significantly to 9.5% and 12.3% on 3-week and 3-month follow-up examinations, respectively (P<0.05). A statistically significant increase was observed in 2 of the 3 parts of the Shriners Hospital Upper Extremity Evaluation: spontaneous use (P<0.05) and the ability of the involved limb to grasp and release (G/R) (P<0.05). CONCLUSIONS: These preliminary results suggest that FU without rehabilitation improves the spontaneous use and function of the affected upper limb. In children with hemiplegia, this approach may be an economically viable means of upper limb treatment that has no side effects. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions to Authors for complete description of level of evidence.

Upper limbs function after intrathecal baclofen therapy in children with secondary dystonia.

BACKGROUND: Different studies show the efficacy of intrathecal baclofen therapy (ITB) in patients with secondary dystonia because of cerebral palsy. These studies only report improvements related to dystonia reduction; however, none of them have assessed whether such benefit is reflected in limb function. The purpose of our study is to determine whether the effects ITB therapy in patients with secondary dystonia to cerebral palsy, in addition to reducing dystonia, may also improve upper limb function. METHODS: Eleven patients with secondary dystonia, classified as levels 3 and 4 of the Gross Motor Function Classification System, were treated with ITB. The mean age at implant was 11.3 (SD+/-3.02) years.Before treatment and 12 months after implant, the patients were evaluated by the Melbourne Assessment of Unilateral Upper Limb and the Barry Albright scale to assess upper limb function and dystonia, respectively. RESULTS: We found a statistically significant improvement in both scales. The Melbourne scale total percentage score, for both limbs, increased in all patients (P<0.05). Dystonia assessed by the Barry Albright scale scale decreased significantly by 15% from baseline to 12 months follow-up (P<0.05). CONCLUSIONS: In patients with secondary dystonia treated with ITB, functional improvement of the upper limbs was observed in addition to dystonia reduction. In patients with secondary dystonia, ITB is a treatment that aims to achieve a general reduction of dystonia; this study want to show the influence that this reduction has to functional ability of patient. LEVEL OF EVIDENCE: Therapeutic study: level 4.

Effect of intrathecal baclofen on dystonia in children with cerebral palsy and the use of functional scales.

BACKGROUND: The literature available shows that spasticity in patients with cerebral palsy (CP) is reduced by intrathecal baclofen (ITB) treatment, and various studies suggest that this treatment can also be used in dystonic patients. The aim of the present study was to evaluate dystonia treated with ITB in children with CP. METHODS: Data of 19 patients affected by dystonia as an outcome of infant CP in patients belonging to level V of Gross Motor Function Classification System treated with ITB were collected. The mean age at implant is 8.49 years.The patients are assessed using Barry-Albright Scale and Burke-Fahn-Marsden Scale before treatment and at 3, 6, and 12 months postimplant. RESULTS: The results showed a statistically significant improvement (P < 0.001) in the total scores of the 2 scales after just 3 months of treatment, an improvement that was maintained for the 1-year period of follow-up. The results also revealed a reduction in dystonias, an improvement in posture, and an easing of the task of the caregivers in managing the patient as a result of treatment with ITB. CONCLUSIONS: In patients belonging to level V of Gross Motor Function Classification System and treated with ITB, a decrease in frequency and severity of dystonia is observed. This improvement eases caregiver in patient management. LEVEL OF EVIDENCE: Therapeutic Level IV.

Upper limb function after intrathecal baclofen treatment in children with cerebral palsy.

BACKGROUND: The literature shows that intrathecal baclofen (ITB) treatment in patients with cerebral palsy (CP) is able to reduce spasticity. The purpose of this work is to evaluate the motor function of the upper limbs in patients with CP treated with ITB. METHODS: A consecutive series of 20 patients with spastic CP (mean age at implant, 11.4 years) implanted with pumps in our center was studied. These patients were classified using the Gross Motor Function Classification System. The patients were followed up over a 12-month period for assessment of the upper limb function with the Melbourne Assessment of Unilateral Upper Limb Function scale. RESULTS: The data show a reduction of upper limb spasticity in all 20 patients (P < 0.05). The Melbourne scale shows a statistically significant improvement of the total score (P < 0.05) and an improvement of the subskills of range of movement, target accuracy, and fluency. Twenty-five percent of patients showed a clinically significant improvement. CONCLUSION: The subjects with CP of different degrees of severity had an improvement in the quality of the upper limb function and showed overall satisfaction with the results achieved. The study also shows the importance of evaluating the quality of upper limb function in children with CP treated with ITB therapy.

The use of intrathecal baclofen pump implants in children and adolescents: safety and complications in 200 consecutive cases.

OBJECT: The authors investigated the efficacy of intrathecal baclofen therapy, analyzing the complications and risk factors in 200 consecutive patients who received pump implants. METHODS: The patient population included 200 patients (mean age 13.7 +/- 5.68 years). The follow-up duration varied from 13.07 to 87.50 months (mean 50.71 months). RESULTS: The mean Ashworth Scale, Barry-Albright Dystonia Scale, clonus, and spasm scores decreased postoperatively. Overall, 31% of patients experienced complications as follows: 11% had cerebrospinal fluid leakage, 7% had catheter-related problems, 7.5% suffered infections; 5.5% of patients had more than one complication. CONCLUSIONS: The authors found that the onset of at least one complication is statistically more likely in patients with Ashworth Scale scores higher than 3 and an age of 10 years or younger. A reduction in the incidence of infection from 10 to 4.8% by the end of the study period appears to be correlated with the switch in technique to subfascial instead of subcutaneous pump implantation and the adoption of a new preoperative prophylaxis protocol in the last 51 patients. There were no statistically significant correlations between the onset of complications and patient weight, ambulatory status, or the presence of dystonia or cerebral palsy.