Debabrata Ghosh

Neural targets for relieving parkinsonian rigidity and bradykinesia with pallidal deep brain stimulation

Clinical evidence has suggested that subtle changes in deep brain stimulation (DBS) settings can have differential effects on bradykinesia and rigidity in patients with Parkinsons disease. In this study, we first investigated the degree of improvement in bradykinesia and rigidity during targeted globus pallidus DBS in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus macaques. Behavioral outcomes of DBS were then coupled with detailed, subject-specific computational models of neurons in the globus pallidus internus (GPi), globus pallidus externus (GPe), and internal capsule (IC) to determine which neuronal pathways when modulated with high-frequency electrical stimulation best correlate with improvement in motor symptoms. The modeling results support the hypothesis that multiple neuronal pathways can underlie the therapeutic effect of DBS on parkinsonian bradykinesia and rigidity. Across all three subjects, improvements in rigidity correlated most strongly with spread of neuronal activation into IC, driving a small percentage of fibers within this tract (<10% on average). The most robust effect on bradykinesia resulted from stimulating a combination of sensorimotor axonal projections within the GP, specifically at the site of the medial medullary lamina. Thus the beneficial effects of pallidal DBS for parkinsonian symptoms may occur from multiple targets within and near the target nucleus.

Lateral sinus thrombosis associated with mastoiditis and otitis media in children: a retrospective chart review and review of the literature.

The authors describe the clinical features and management of lateral sinus thrombosis associated with mastoiditis and otitis media in children. Of 475 patients with mastoiditis and otitis media, 13 (2.7%) had lateral sinus thrombosis identified by magnetic resonance imaging/magnetic resonance venography (n = 11) and angiography (n = 2). Clinical features included headache, vomiting, fever, diplopia, papilledema, sixth nerve palsy, seventh nerve palsy, and unilateral cerebellar ataxia. All patients received antibiotics for 1 to 8 weeks. Four patients underwent mastoidectomy alone, 5 mastoidectomy with concurrent myringotomy and ventilation tube, and 1 myringotomy with tube without mastoidectomy. Three underwent anticoagulation for 6 months (1 had heterozygous factor V Leiden mutation). All survived; deafness occurred in 5 patients (4 transient, 1 persistent). Magnetic resonance imaging/magnetic resonance venography should be obtained in any child with otitis media having features of raised intracranial pressure and/or focal neurodeficits to rule out lateral sinus thrombosis. Antibiotics and mastoidectomy are essential in management. A hypercoagulable state may predispose to lateral sinus thrombosis.

Complications of Intrathecal Baclofen Pumps in Children: Experience from a Tertiary Care Center

Background/Aims: Intrathecal baclofen (ITB) therapy is useful in treating spasticity and dystonia but it has many complications, more so in children. The main aim of the study was to look at the complications of ITB pumps in children with the goal of future prevention. Methods: Charts of all patients ≤21 years with an ITB pump, implanted by a single pediatric neurosurgeon, at a single center, between 1996 and 2011 were reviewed retrospectively. Data regarding an ITB test trial were also recorded. Results: During 1996-2011, 119 children (mean age 13.2 years) underwent ITB pump placement; 84% had spastic quadriplegic cerebral palsy. The gross motor function classification system level was ≥4 for most. The pump was removed in 5 (4.2%) patients due to inefficacy. The mean follow-up was 38 months. Mechanical complications requiring pump and/or catheter revision occurred in 19.3% and infections in an additional 21.8%. Seven patients (6%) had meningitis. No complication was noted after 72 months of initial pump insertion, even after pump reinsertion. Conclusion: There is a need for better infection control as well as better pump, catheter and surgical technology to lower the complications of ITB pumps in children.

Subdural Hematoma in Infants Without Accidental or Nonaccidental Injury Benign External Hydrocephalus, a Risk Factor

Benign external hydrocephalus (BEH) is considered a self-limiting condition in infants. Subdural hematoma (SDH) in infants without a history of trauma indicates nonaccidental injury (NAI). The authors studied whether SDH can complicate BEH without apparent trauma. Out of 45 children younger than 3 years with nontraumatic SDH, 9 (7 boys) with mean age 6 months had BEH as risk factor. Symptoms included increasing head size (8), fussiness, and irritability (3). Three had up-gaze restriction, 1 axial hypotonia, and 6 normal examination. Neuroimaging showed prominent extra-axial spaces; SDH was bilateral (6), subacute (5). Other etiological workup for SDH was negative except NAI in 1. Two required evacuation of SDH and subdural–peritoneal shunt; others managed conservatively. Development was normal in 8 on follow-up. On follow-up imaging of 8, SDH completely resolved in 3, markedly reduced in 3, and remained stable in 2. BEH is a risk factor for SDH in infants, thus not always benign.

Neurological complications following pediatric liver transplant.

Objective: We studied neurological complications (NCs) after liver transplantation (LT) in children. Methods: We performed an institutional review board–approved retrospective review of patients with LT ⩽21 years during a period of 30 years (1980–2010). NCs were classified as early (within 3 months post-LT) and delayed (beyond 3 months post-LT). Results: Of 65 children with LT, 20 (30.7%) had NCs; 16 were girls. Mean age was 11.8 ± 5.9 years. Early NCs were found in 13.8% (9/65) of the patients: seizures in 7 and encephalopathy in 2. Abnormal neuroimaging findings were posterior reversible leukoencephalopathy syndrome (1), intracranial hemorrhage (1), mild cerebral edema (1), and bilateral basal ganglia T1W hyperintensities in magnetic resonance imaging (1). On follow-up, there were 3 deaths (unrelated to NCs). One with intracranial hemorrhage had residual hemiparesis and was taking a long-term antiepileptic drug. Late NCs are found in 16.9% (11/65) of the patients: seizures in 4, headache in 4, encephalopathy in 3 (1 had seizures in addition), and paresthesias caused by possible small-fiber neuropathy in 1. Abnormal neuroimaging findings were hypoxic-ischemic encephalopathy (1), encephalomalacia caused by old hemorrhage (1), and hyperintensity of the posterior periventricular white matter in magnetic resonance imaging (1). On follow-up, all of the patients survived; 1 had papilledema with secondary optic atrophy requiring optic nerve sheath fenestration and 1 needed long-term antiepileptic drug. Conclusions: NCs are common in children after LT, seizures being the most common. In contrary to the previous studies, we found delayed complications more often than early complications. Early detection and appropriate management of NCs is important.

Hirayama Disease in Children From North America

Hirayama disease has been mainly reported from Asia; only a few cases are from the Western hemisphere, particularly North America. This is a retrospective chart review of patients < 18 years, diagnosed with Hirayama disease from a single center over 10 years. We diagnosed 6 children (4 boys), 15.1 ± 1.2 years of age. Symptom onset was 3 months to 3 years before presentation. All had unilateral or bilateral asymmetric distal upper extremity weakness without objective sensory loss. Oblique amyotrophy and cold paresis were noted in 5. On electromyography, acute-on-chronic denervation was most frequently noted in cervical-8 (C8) and thoracic-1 (T1) myotomes followed by cervical-7 (C7) myotome in both upper limbs, sparing C5–C6 myotomes. Cervical magnetic resonance imaging (MRI) was abnormal in 3. Symptoms progressed over a mean of 16.5 months. Treatment consisted of placement of cervical collar. Heightened awareness of this entity among pediatric neurologists in North America will lead to early diagnosis and intervention, avoiding unnecessary investigations.

Holocord spinal epidural abscess

Spinal epidural abscess is rare in infants and leads to major permanent neurological deficits if the condition is left untreated. Holocord epidural abscess is extremely rare. We report a patient with methicillin-resistant Staphylococcus aureus septicemia presenting with pneumonia, retroperitoneal abscess, and epidural abscess. A 7-month-old previously healthy girl presented with fever, irritability, tachypnea for 4 days and decreased movement of the right lower limb for 1 day. Magnetic resonance imaging of the spine demonstrated an extensive epidural abscess from second cervical to fifth lumbar vertebrae without osteomyelitis or discitis. The epidural abscess was treated with intravenous antibiotics for 6 weeks. At 3 months follow-up, no neurological deficits were present. Only a few case reports of holocord epidural abscess in children have been published. We present a case of conservatively treated holocord spinal abscess in an infant.

Headache in Children with Tourette Syndrome

OBJECTIVE The authors analyzed the frequency of occurrence of headaches in children and adolescents with Tourette syndrome (TS) to address their possible inclusion as a comorbidity. STUDY DESIGN Using a prospective questionnaire, administered directly, we interviewed a total sample size of 109 patients with TS ≤ 21 years of age. The questionnaires were then analyzed according to the International Headache Societys diagnostic criteria. RESULTS We found headaches to be present in 55% of the patients, with the 2 most common headache types being migraine headaches and tension-type headaches. The rate of migraine headache within the TS group was found to be 4 times greater than that of the general pediatric population, as reported in the literature. In addition, the rate of tension-type headache was found to be more than 5 times greater than that of the general pediatric population. CONCLUSIONS Overall, the high rates of migraine and tension-type headache within this population support the proposition that headaches are a comorbidity of TS.

Primary Myoclonus-Dystonia A Diagnosis Often Missed in Children

Primary myoclonus-dystonia is a childhood-onset autosomal-dominant movement disorder with myoclonic jerks and dystonia. The authors report 9 children (4 boys, 5 girls) with myoclonus-dystonia from 8 families seen over a 4-year period at Cleveland Clinic. The mean age of onset of symptoms was 2.8 years, but the diagnosis was made at a mean of 7.3 years. Myoclonus was the presenting symptom in 8 children. A known pathogenic mutation in the ε-sarcoglycan gene (SGCE) was identified in 4 of the 9 children, and 2 other children had novel mutations in the same gene. Good response to trihexyphenidyl and clonazepam was seen. Two patients underwent deep brain stimulation surgery of the bilateral globus pallidus pars interna. In 7 children, the diagnosis of myoclonus-dystonia was not considered by the referring child neurologists, which led to extensive investigations and a delay in the final diagnosis. In this report, the authors highlight the need for increased awareness of this entity among child neurologists.

Deep Brain Stimulation in Children with Dystonia: Experience from a Tertiary Care Center

Objective: To investigate the efficacy and safety of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in children with dystonia. Methods: Retrospective chart review of patients (≤21 years) with dystonia who underwent GPi DBS. Outcome measures were assessed by the Burke-Fahn-Marsden Dystonia Rating (BFMDR) movement and disability scales pre- and post-DBS. Results: Eight patients underwent DBS; mean age of onset was 7.5 ± 4.8 years (7 were male). Mean age at DBS was 14.1 ± 4.6 years. Etiology of dystonia was primary in 6 patients and secondary in 2. There was significant improvement of BFMDR movement as well as BFMDR disability scales in 6 patients with primary dystonia with modest improvement in those scales in 2 patients with secondary dystonia. Hardware-related problems were observed in 2 and infection was noted in 1. Conclusions: GPi DBS is an effective and safe therapy in pediatric patients with primary as well as selected cases of secondary dystonia.