Thiago Bortholin

Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks

Hereditary spastic paraplegia comprises a wide and heterogeneous group of inherited neurodegenerative and neurodevelopmental disorders resulting from primary retrograde dysfunction of the long descending fibers of the corticospinal tract. Although spastic paraparesis and urinary dysfunction represent the most common clinical presentation, a complex group of different neurological and systemic compromise has been recognized recently and a growing number of new genetic subtypes were described in the last decade. Clinical characterization of individual and familial history represents the main step during diagnostic workup; however, frequently, few and unspecific data allows a low rate of definite diagnosis based solely in clinical and neuroimaging basis. Likewise, a wide group of neurological acquired and inherited disorders should be included in the differential diagnosis and properly excluded after a complete laboratorial, neuroimaging, and genetic evaluation. The aim of this review article is to provide an extensive overview regarding the main clinical and genetic features of the classical and recently described subtypes of hereditary spastic paraplegia (HSP).

Teaching NeuroImages: An extremely rare cause of treatable acute encephalopathy

A 32-year-old Brazilian man presented with subacute encephalopathy and gait instability. Examination showed generalized dystonia and lethargy. Brain MRI showed diffuse symmetrical leukoencephalopathy without changes in the basal ganglia (figure). Genetic analysis revealed heterozygous mutations c.74dupT and c.980-14A<G in the SLC19A3 gene. There was marked neurologic improvement after high doses of thiamine replacement.

Motor neuron disease in inherited neurometabolic disorders

Inherited neurometabolic disorders represent a growing group of inborn errors of metabolism that present with major neurological symptoms or a complex spectrum of symptoms dominated by central or peripheral nervous system dysfunction. Many neurological presentations may arise from the same metabolic defect, especially in autosomal-recessive inherited disorders. Motor neuron disease (MND), mainly represented by amyotrophic lateral sclerosis, may also result from various inborn errors of metabolism, some of which may represent potentially treatable conditions, thereby emphasizing the importance of recognizing such diseases. The present review discusses the most important neurometabolic disorders presenting with motor neuron (lower and/or upper) dysfunction as the key clinical and neuropathological feature.

Familial progressive bilateral facial paralysis in Finnish type hereditary amyloidosis

A 60-year-old Brazilian man gave a 20-year history of progressive bilateral facial weakness. He was known to have lattice corneal dystrophy. His father, two paternal uncles and a son had similar neurological problems. His father was born in Portugal and his paternal grandmother was born in Finland. On examination, there was severe bilateral facial weakness (figure 1). Neurophysiology studies found bilateral axonal facial neuropathy but …

Postictal thoracocervicofacial purpura

A 28-year-old Brazilian man presented with a 2-hour history of headache and skin lesions in the shoulder girdle, face and upper trunk. Two hours before, he had a generalised tonic-clonic seizure, his third since being diagnosed with genetic generalised epilepsy 1 year before. Each previous episode had been accompanied by the same pattern of skin lesions, which improved after 48 hours. On examination, …

Collagen type VI-related myopathy

A 15-year-old Brazilian boy presented with slowly progressive infancy-onset global amyotrophy and limb-girdle pattern of weakness. His perinatal history and prior motor milestones were normal, and there was no relevant family history. On examination, he had a scoliosis, multiple joint contractures with distal hypermobility, follicular hyperkeratosis and keloid scar formation (figure 1). Figure 1 Examination findings in collagen type VI-related myopathies. (A) Marfanoid habitus and marked proximal and distal upper limb muscle atrophy with multiple …

Early-onset axonal Charcot-Marie-Tooth disease due to SACS mutation

Axonal Charcot-Marie-Tooth disease (CMT) represents an expanding group of inherited motor and sensory neuropathies in clinical practice. SACS-gene related disorders have been associated with complex neurological phenotypes of early-onset cerebellar ataxia, spastic-ataxia, spastic paraplegia, demyelinating neuropathy and variable ophthalmological, cognitive and psychiatric disturbances, but never related to pure axonal neuropathy phenotypes. Two unrelated Brazilian men with early-onset axonal CMT-like presentations associated with SACS gene mutations are presented. Both patients presented with pure sensorimotor axonal neuropathy without cerebellar ataxia, spastic paraplegia or other systemic and neurological involvement. Classical neuroimaging findings observed in other sacsinopathies were observed in both cases. Homozygous pathogenic mutations were found in SACS gene in both patients. SACS gene mutations can be associated with pure axonal sensorimotor neuropathy without other neurological features, but with typical neuroimaging features of other sacsinopathies, disclosing the importance of performing neuroimaging studies in patients with suspected axonal CMT.

Letter re: Acute intermittent porphyria-related leukoencephalopathy

We read with interest the article by Kevelam et al.1 Current neurogenetic knowledge continues to grow with new genotypes associated with classical clinical syndromes and new phenotypes associated with shocking genetic and metabolic mechanisms, especially in inherited neurometabolic disorders and leukodystrophies. The authors defined a new clinical spectrum of neurologic phenotypes associated with mutations in the HMBS gene,1 which can be summarized as follows: (1) autosomal dominant acute intermittent porphyria2; (2) autosomal recessive severe encephalopathy with early childhood fatality3; (3) autosomal recessive early-onset leukodystrophy with spastic ataxia and optic atrophy.1

Teaching Neuro Images : Early-onset dementia and demyelinating neuropathy disclosing cerebrotendinous xanthomatosis

A 40-year-old woman presented with a 5-year history of numbness in hands and feet, apathy, compulsive behavior, and aggression towards others. Medical history disclosed juvenile-onset cataracts. Examination disclosed tendinous xanthoma. Electroneuromyography disclosed sensorimotor demyelinating polyneuropathy. Neuroimaging studies showed global cortical atrophy. Tc-99m brain SPECT scan showed marked hypoperfusion involving the frontal and temporal lobes (figure). Plasma cholestanol levels and bile alcohol glycoconjugates were elevated, enabling a diagnosis of cerebrotendinous xanthomatosis (CTX).

Teaching Neuro Images : MR neurography for the diagnosis of hypertrophic neuropathies

A 25-year-old woman presented with a 10-year history of frequent falls and deafness. Her mother had a similar neurologic picture. Examination showed peroneal amyotrophy, pes cavus, and hearing loss. Magnetic resonance (MR) neurography showed diffuse nerve enlargement in the lower limbs (figure). Genetic analysis revealed heterozygous mutation c.82T>C (p.Trp28Arg) in the PMP22 gene, defining diagnosis of Charcot-Marie-Tooth disease (CMT) type 1A.