Hanene Benrhouma

Movement disorders in neuro-metabolic diseases

Inborn errors of metabolism (IEM) are a group of genetic disorders characterized by dysfunction of an enzyme or other protein involved in cellular metabolism.(1) Most IEMs involve the nervous system (neuro-metabolic diseases or NMD). NMD often present with a complex clinical picture: psychomotor retardation and/or regression, pyramidal signs, ataxia, hypotonia and epilepsy and movement disorders.(1) Movement disorders are more frequently part of this complex picture than a predominant symptom, however in some instances the clinical picture may be summarized in an invalidating movement disorder.(2) On a phenomenology basis, one can distinguish eight main types of movement disorders: dystonia and athetosis, chorea, tremor with or without parkinsonism, ballismus, myoclonus, tics and stereotypies. Most of these abnormal involuntary movements generate from a dysfunction or a lesion in the basal ganglia, excepting myoclonus, the origin of which can vary (cortical, brainstem, basal ganglia, spinal and even peripheral nervous system).(3) Classically the most frequently observed movement disorders in NMD are: dystonia, myoclonus, chorea, tremor and parkinsonism (Fig. 1). The primary goal of this article is, departing from the literature and a large personal series, to describe the types of movement disorders most frequently observed in NMD and to discuss their clinical value in the setting of specific types of NMD.

Anti-Ma2-encephalitis in a 2 year-old child: A newly diagnosed case and literature review

BACKGROUND Anti-Ma2-associated encephalitis is a rare paraneoplastic neurological syndrome characterized by isolated or combined limbic, diencephalic, or brainstem dysfunction. It is rarely reported in children. CASE STUDY We describe the clinical data of a 2-year-old girl referred to our department for refractory focal seizures associated with fever, followed by behavioural changes, speech disturbances and confusional episodes. Brain magnetic resonance imaging (MRI) showed left temporoparietal brain involvement. Haematological, biochemical and infectious evaluations were unremarkable. Autoimmune encephalitis was suspected. Paraneoplastic antibodies tests showed positive results for anti-Ma2 antibodies. Screening for underlying tumour was negative. Immunomodulatory treatment was administrated. The patient showed improvement of vigilance and behaviour. However, she kept refractory epilepsy. CONCLUSION Although poor response to immunotherapy, early diagnosis and appropriate treatment of this disorder may prevent irreversible sequelae.

Secondary parkinsonism with bilateral involvement of substantia nigra in cerebral malaria

Cerebral malaria is characterized by various non-specific neurologic features with usually diffuse cerebral edema on magnetic resonance imaging. We report on an exceptional case of cerebral malaria with isolated parkinsonism and bilateral substantia nigra involvement. We discuss the pathophysiology leading to involvement of substantia nigra and treatment options.

Pyridoxine-dependent epilepsy: A novel mutation in a Tunisian child

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive metabolic disease characterized by seizures in neonates or infants, which is unresponsive to antiepileptic drugs but controlled by pyridoxine. Without prompt treatment, continued seizures and severe encephalopathy result. Mutations in the ALDH7A1 gene encoding α-amino-adipic semialdehyde (α-AASA) dehydrogenase (antiquitin) have been identified as the cause of PDE. We report on a novel ALDH7A1 mutation in a Tunisian child with PDE.

Elevated aspartate aminotransferase and lactate dehydrogenase levels are a constant finding in PLA2G6-associated neurodegeneration.

I. Kraoua, M. Romani, D. Tonduti, H. BenRhouma, G. Zorzi, F. Zibordi, A. Ardissone, N. Gouider-Khouja, I. Ben Youssef-Turki, N. Nardocci and E. M. Valente Department of Child and Adolescent Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis, Tunisia, IRCCS Casa Sollievo della Sofferenza, Mendel Laboratory, San Giovanni Rotondo, Italy, Child Neurology Department, Neurological Institute C. Besta Foundation IRCCS, Milan, Italy and Section of Neurosciences, Department of Medicine and Surgery, University of Salerno, Salerno, Italy

Mixed movements disorders as an initial feature of pediatric lupus

UNLABELLED Systemic lupus erythematosus (SLE) is an immunologic disease of the early adulthood. In children, SLE is rare and neurological onset is uncommon. We report on an observation of pediatric lupus in heterozygous twins revealed by mixed movement disorders. CASE REPORT An 8-year-old boy, born to non consanguineous parents, with a family history of depression and a personal history of macular eruption, inflammatory polyarthralgias and a recurrent angina presented with acute movement and mood disorders. Neurological exam showed mild generalized choreic movements with motor and vocal tics. Antinuclear antibodies were positive. Brain MRI was normal. One year after, his twin brother presented with the same features. DISCUSSION Movement disorders are described in pediatric lupus but are unusual as inaugural features of the disease. In SLE, movement disorders such as chorea are usually reported. However, Tics seem to be exceptional. Pathophysiology remains unclear. Early onset and familial form support genetic implication in the pathogenesis of lupus. CONCLUSION Immune-mediated movement disorders such as in SLE are an established cause of acute movement disorders in child.

Acquired demyelinating syndromes of the central nervous system in children: study of a cohort of 47 cases

Multiple sclerosis (MS) is a chronic neurological disorder defined by recurrent episodes of central nervous system (CNS) demyelination, ultimately culminating in physical and cognitive disability. While it is rare in the paediatric population, MS in children is likely to have a profound impact on their lifetime academic, social, and vocational achievements. The advent of disease-modifying therapies for MS and the recent evidence of improved long-term outcome, associated with early initiation of therapy, emphasize the need for prompt diagnosis and coordinated care for children affected with MS.

Pediatric Multiple Sclerosis in Tunisia: A Retrospective Study over 11 Years

Introduction Pediatric multiple sclerosis (pMS) is a rare demyelinating disorder with an onset before the age of 18 years. In this study, we aimed to investigate the characteristics of pMS in Tunisian children. Patients and Methods We conducted a retrospective study over 11 years (2005–2016) including all patients diagnosed with pMS according to the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria of 2012 and followed up in a tertiary care research center. Epidemiological, clinical, neuroimaging, laboratory, and therapeutic data were collected and analyzed. Results There were 21 patients. The male-female ratio was 1 : 3. Mean age at onset was 11 years (range: 3–17 years). Three patients had type 1 diabetes. Polyfocal presentation was preponderant (81%) with motor dysfunction in 57% of patients. Paroxysmal dystonia was noticed in 24%. All patients were diagnosed with relapsing-remitting form. Interferon beta was prescribed in 80% with a reduction of annual relapse rate. Conclusion The annual incidence of pMS in Tunisian children aged below 18 years could be estimated as 0.05 per 100,000. Singular features in our cohort were the frequent association with type 1 diabetes and the increased occurrence of dystonia. Greater awareness of pMS may be helpful to improve management strategies of children and their families.

Lésion mésencéphalique avec rehaussement annulaire : tuberculome ou toxoplasmose ?

Cette fillette de 18 mois, sans antécédents familiaux ni personnels notables, avait présenté brutalement au réveil une impotence fonctionnelle de l’hémicorps gauche avec asymétrie faciale. Il n’y avait pas de contexte traumatique ou infectieux. L’examen clinique pratiqué quelques heures après l’installation des troubles a objectivé une hémiparésie gauche flasque, un signe de Babinski à gauche et une parésie faciale périphérique droite. L’état général était conservé et les constantes hémodynamiques étaient stables. Le reste de l’examen clinique était sans particularités. Devant ce syndrome alterne de type Millard-Gübler de survenue brutale, un accident vasculaire cérébral (AVC) protubérantiel a été suspecté. Les examens biologiques (numération-formule sanguine, glycémie, vitesse de sédimentation, taux de protéine C réactive (CRP), ionogramme sanguin, transaminases, gamma-glutamyl transpeptidase, bilirubine totale et conjuguée, azotémie, créatininémie) se sont avérés normaux. Une imagerie par résonance magnétique (IRM) encéphalique a été réalisée 36 heures après l’installation des troubles (fig. 1). Cet examen comportait des coupes en pondération T2, FLAIR, diffusion, perfusion et T1 sans et avec injection intraveineuse de gadolinium.

A Case of Progressive Chorea Resulting From GLUT1 Deficiency

Glucose transporter 1 (GLUT1) deficiency syndrome is caused by solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) gene mutations. These mutations cause impaired glucose transports into the brain, leading to cerebral energy deficiency. This disease’s most common form is typically characterized by infantile-onset, intractable epileptic encephalopathy, acquired microcephaly, psychomotor delay, and hypoglycorrhachia. Recently, the clinical spectrum of GLUT1 deficiency syndrome has been broadened, making the diagnosis challenging in clinical practice.