Aida Rouissi

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.

Postencephalitic parkinsonism and selective involvement of substantia nigra in childhood

Parkinsonism is a rare complication of encephalitis in childhood. Association to an isolated involvement of substantia nigra is exceptional. Mechanisms of nigral cells neurotropism remain hypothetic. We report on three children presenting with postencephalitic parkinsonism and selective involvement of substantia nigra, with literature review and we discuss pathogenic mechanisms.

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.

3-Phosphoglycerate Dehydrogenase Deficiency: Description of Two New Cases in Tunisia and Review of the Literature

3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is a rare autosomal recessive disorder of serine biosynthesis. It is typically characterized by congenital microcephaly, intractable seizures of infantile onset, and severe psychomotor retardation. Diagnosis is suspected on decreased l-serine levels in plasma and cerebrospinal fluid (CSF) and confirmed by genetic study. Early diagnosis in index cases allows supplementation in serine and prevention of fixed lesions. Prenatal diagnosis and genetic counseling allows prevention of secondary cases. We report on the two first unrelated Tunisian families with 3-PGDH deficiency confirmed by biochemical and genetic study. We discuss clinical, biochemical, imaging, electroencephalographic, and therapeutic aspects and review the literature.

Joubert syndrome and related disorders: Report of five Tunisian cases

Joubert syndrome and Joubert syndrome related disorders are rare autosomal recessive disorders, clinically and genetically heterogeneous characterized by cerebellar vermis hypoplasia and a peculiar midbrain-hindbrain malformation the “molar tooth sign”. Clinical picture is characterized by hypotonia, ataxia, developmental delay, abnormal eye movements and occasionally by abnormal respiratory pattern in the neonatal period. Combination of additional features, such as polydactyly, ocular coloboma, retinal dystrophy, renal disease, hepatic fibrosis, encephalocele, and other brain malformations define various clinical subtypes. We report five cases (belonging to four families) with associated elastopathy in one family. We discuss clinical heterogeneity in particular the unusual association to elastopathy in one family and absence of abnormal neonatal respiratory pattern in all five cases.

Early Life Epilepsy and Episodic Apnea Revealing an ATP1A3 Mutation: Report of a Pediatric Case and Literature Review

Abstract ATP1A3 mutations have now been recognized in infants, children, and adults presenting with a diverse group of neurological phenotypes, including rapid‐onset dystonia‐parkinsonism, alternating hemiplegia of childhood, and most recently, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome. The phenotypic spectrum of ATP1A3‐related neurological disorders continues to expand. In this case study, we report on early life epilepsy with episodic apnea potentially secondary to ATP1A3 mutation in a Tunisian child.

First report of an unusual novel double mutation affecting the transcription repression domain of MeCP2 and causing a severe phenotype of Rett syndrome: Molecular analyses and computational investigation

Rett syndrome is an X-linked neurodevelopmental disorder that develops a profound intellectual and motor disability and affects 1 from 10 000 to 15 000 live female births. This disease is characterized by a period of apparently normal development until 6-18 months of age when motor and communication abilities regress which is caused by mutations occurred in the X-linked MECP2 gene, encoding the methyl-CpG binding protein 2. This research study reports a molecular analysis via an exhaustive gene sequencing which reveals an unusual novel double mutation (c.695 G > T; c.880C > T) located in a highly conserved region in MECP2 gene affecting the transcription repression domain (TRD) of MeCP2 protein and leading for the first time to a severe phenotype of Rett syndrome. Moreover, a computational investigation of MECP2 mutations demonstrates that the novel mutation c.695 G > T is highly deleterious which affects the MeCP2 protein showing also an adverse impact on MECP2 gene expression and resulting in an affected folding and decreased stability of MECP2 structures. Thus, the altered TRD domain engenders a disrupted process of MECP2 functions. Therefore, this is the first study which highlights a novel double mutation among the transcription repression domain (TRD) of MeCP2 protein in Rett patient with a severe clinical phenotype in North Africa region.

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.