Unusual Calcification in Intramedullary Epidermoid Cyst.

BACKGROUND: Calcified intraspinal epidermoids are a rare entity. We discuss the various pathogenesis and the clinical implication of such a finding during surgery. CASE DESCRIPTION: A 32-year-old female presented with progressive spastic paraparesis with incontinence. Imaging showed an unusual intralesional calcification, which was removed. Postoperatively she had no fresh deficits. CONCLUSIONS: To our knowledge this is the first reported case of spinal intramedullary epidermoid with intralesional calcification.

Motor Cortex Mapping in Patients With Hepatic Myelopathy After Transjugular Intrahepatic Portosystemic Shunt.

RATIONALE AND OBJECTIVES: As a special movement disorder, hepatic myelopathy (HM) is characterized by spastic paraperesis and may be secondary to transjugular intrahepatic portosystemic shunt (TIPS). The prediction and diagnosis of HM is difficult due to largely unknown neuropathological underpinnings and a lack of specific biomarkers. We aimed to delve into the alterations in motor system of HM patients' brain and their potential clinical implication. MATERIAL AND METHODS: Twenty-three patients with HM and 23 without HM after TIPS and 24 demographically matched healthy controls were enrolled. High-spatial-resolution structural imaging and functional data at rest were acquired. Motor areas were included as seed regions for functional connectivity analysis. Then, we performed brain volume analysis. RESULTS: We found decreased right supplementary motor area (SMA)-seeded functional connectivity with bilateral insula, thalamus and midbrain, left cerebellum and middle temporal gyrus, and right middle cingulate gyrus in HM compared to non-HM patients (p < 0.001). The right insula revealed decreased volume (p < 0.001), and white matter volume reduced in the right corona radiata beneath the right SMA (p < 0.001) in HM relative to non-HM patients. Furthermore, the strength of right SMA-seeded connectivity with insula was positively correlated with folic acid level in HM patients (r = 0.60, p = 0.03), showing an accuracy of 0.87 to distinguish HM from non-HM. CONCLUSION: Our study demonstrates the HM-specific dysconnectivity with an anatomical basis, and its correlation with laboratory findings and diagnostic value. Detecting these abnormalities might help to predict and diagnose post-TIPS HM.

CAPN1 mutations: Expanding the CAPN1-related phenotype: From hereditary spastic paraparesis to spastic ataxia.

AIMS AND OBJECTIVE: To characterize the phenotype of CAPN1 (SPG76) mutations in patients diagnosed with hereditary spastic paraplegia (HSP). BACKGROUND: The CAPN1 gene, located on chromosome 11q13.1, is a protein-coding gene involved in neuronal plasticity, migration, microtubular regulation and cerebellar development. Several families with CAPN1 mutations have recently been reported to present with autosomal recessive (AR) HSP and/or ataxia. METHOD: Patients with HSP were identified through neurological and genetic clinics with detailed phenotyping. Whole exome sequencing revealed novel pathogenic CAPN1 mutations in four patients from 3 families. RESULTS: Affected families were of Turkish, Japanese, and Punjabi descent and all were consanguineous. Onset of spastic paraplegia in the four patients was between 20 and 37 years. Two also had mild ataxia. Three different novel, homozygous mutations in CAPN1 were found: c.2118+1G > T, c.397C > T, c.843+1G > C. The patient with the earliest onset also manifested profound muscle weakness, likely related to a second homozygous mutation in DYSF (dysferlinopathy). CONCLUSIONS: The phenotype of AR CAPN1 mutations appears to be spastic paraplegia with or without ataxia; onset is most commonly in adulthood. Eye movement abnormalities, skeletal defects, peripheral neuropathy and amyotrophy can sometimes be seen. Occasionally, patients can present with ataxia, illustrating the genotypic and phenotypic overlap between HSP and spastic ataxia. With the advent of exome sequencing, mutations in more than one gene can be identified, which may contribute to the phenotypic variation, even within a family.

Hirayama disease/cervical flexion-induced myelopathy progressing to spastic paraparesis: A report on three cases with literature review.

Hirayama disease (HD)/cervical flexion-induced myelopathy (CFIM) is a lower motor neuron disease conventionally affecting a single upper extremity. We describe three men progressing after a long stable period to develop severe spastic paraparesis and bladder disturbances as a protracted implication of HD. The age at onset was 20, 24, and 15 years, while the age at presentation was 27, 41, and 57 years, respectively. The second phase of disease progression occurred after 4, 13, and 28 years of stationary period. All had CFIM with characteristic magnetic resonance imaging features as observed during progressive stages. The anterior dural shift extended variably from C4 to D4 levels with a median value of 5 mm and was maximum at C6 to C7 levels, pushing the cord anteriorly causing compression. This study emphasizes the need to recognize this unusual subgroup of HD and mandates long-term follow-up with timely intervention in arresting the progression/improving the deficits.

EEG findings and outcomes of continuous video-EEG monitoring started prior to initiation of seizure treatment in the perinatal stroke.

BACKGROUND: To analyze the findings in the background EEG activity of infants who suffered perinatal stroke. METHODS: Eleven neonates born 2009-2014 diagnosed of ischemic stroke by MRI (three of them with multistroke) underwent continuous video-EEG monitoring. Visual and spectral (power spectrum and coherence) analyses of the background EEG was performed in three moments: 1) Onset of EEG recording (prior to initiate seizure treatment), 2) Post-ictal epoch (1-2 h after the last seizure), and 3) one-two days after seizure control. All children aged 2-6 years underwent neurodevelopmental assessment. RESULTS: Discontinuity, asymmetry, asynchrony, transients, and relative power spectrum in δ and θ frequency bands increased significantly (p < 0.05) in the post-ictal epoch with respect to onset of EEG recording. After seizure control, discontinuity, asynchrony, and θ power spectrum no longer had significant differences with those found at onset of EEG recording. Significant differences between the ischemic and unaffected hemispheres were found in transients and in ß coherence (p = 0.002; p = 0.001, respectively) exclusively in the post-ictal epoch. Seizure burden and time-to-control ranged 5-38 min and 0.5-40 h respectively. Currently, only one child is affected by spastic monoparesis. The intelligence quotients ranged 96-123. CONCLUSIONS: The background EEG can undergo significant changes in the post-ictal epoch due to the seizure activity triggered by the perinatal stroke. Most of these EEG changes involve all brain activity and not exclusively the ischemic hemisphere. Many of these modifications in the EEG background reverse following the seizure control. Video-EEG monitoring allows accurate/immediate diagnosis and rapid/intensive treatment of the stroke-associated seizures.

Spinal cord herniation repair with microstaples: case report.

Idiopathic spinal cord herniation (ISCH) is a relatively rare and frequently misdiagnosed condition. It preferentially affects women and causes progressive thoracic myelopathy that presents as a Brown-Séquard syndrome or as spastic paraparesis. Although its etiology and pathogenesis are controversial, ISCH is characterized by the presence of an anterior dural defect that allows the incarceration of a segment of the cord. Typically, a C-shaped ventral displacement and kinking of the cord are visible on sagittal MRI. Surgery aimed at stopping or reversing myelopathic symptoms is usually recommended for symptomatic patients. Surgical options include reduction of the hernia and direct suturing, or enlargement of the dural defect, with or without patching. Suturing under the cord in a very tight space can be troublesome and may lead to neurological deterioration. The authors present the case of a symptomatic ISCH in which nonpenetrating titanium microstaples were used to close the dural defect after cord reduction. The patient experienced a good outcome, and the follow-up MRI study showed adequate cord repositioning and stability of the suture. The use of microstaples, which allows for an easier and faster dural closure than conventional suturing, is a novel technical adjunct that has not been previously reported for this condition. In addition, microstaples produce minimal metallic artifact that does not hinder the quality of follow-up MR images.

Adrenoleucomielodistrofia como causa de paraparesia espástica en adulto joven. Reporte de caso / Adrenoleukomelodystrophy as a cause of spastic paraparesis in young adult. Case report

La adrenoleucodistrofia ligada al X (X-ALD), trastorno genético progresivo que afecta la sustancia blanca del SNC y la corteza suprarrenal, causa desde insuficiencia adrenal aislada y mielopatia lentamente progresiva hasta desmielinización cerebral devastadora. Presentamos un paciente masculino, 21 años de edad, tabaquista, con trastorno de la marcha de un año de evolución, paraparesia espástica e hiperreflexia en miembros inferiores. El análisis del líquido cefalorraquídeo (LCR) reveló proteinorraquia elevada, resultados negativos de bandas oligoclonales y virus Epstein Barr. Niveles de cortisol, ACTH, ácidos grasos de cadena muy larga en suero, fueron anormales. La RNM cerebral evidenció lesiones en sustancia blanca en región parietooccipital bilateral, comprometiendo el esplenio del cuerpo calloso, que realzaban con gadolinio. En RNM de columna cervical se observó lesión hiperintensa en secuencia T2 a nivel C7. Fue tratado con reemplazo adrenal. Presentamos un caso de X-ALD de inicio en adulto, con retraso en el diagnóstico debido a recursos limitados. Palabras claves: adrenoleucodistrofia ligada al X, paraparesia espástica, ácidos grasos de cadena muy larga, adrenomieloneuropatia

X- Linked adrenoleukodystrophy (X-ALD) is a progressive genetic disorder that affects CNS white matter and adrenal gland cortex, and causes from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. We present a 21 years old male patient, smoker, with one year history of gradually progressive trouble walking, unsteady gait, asymmetric spastic paraparesis, lower extremity deep tendon reflexes were increased. Cerebrospinal fluid (CSF) analysis revealed elevated CSF protein, CSF oligoclonal bands and Epstein Barr virus negative results. Basal cortisol, ACTH and very-long- chain fatty acids in plasma with abnormal results. All other laboratory tests were normal. Cerebral MRI showed parietooccipital white matter abnormalities involving the splenium of the callosum that enhanced with gadolinium. Cervical spinal cord MRI showed a short-segment T2 hyperintense lesion at C7. He was treated with adrenal replacement. We present a case of adult onset X-ALD and diagnostic delay owed to limited resources

Widespread white matter and conduction defects in PSEN1-related spastic paraparesis.

The mechanisms underlying presenilin 1 (PSEN1) mutation-associated spastic paraparesis (SP) are not clear. We compared diffusion and volumetric magnetic resonance measures between 3 persons with SP associated with the A431E mutation and 7 symptomatic persons with PSEN1 mutations without SP matched for symptom duration. We performed amyloid imaging and central motor and somatosensory conduction studies in 1 subject with SP. We found decreases in fractional anisotropy and increases in mean diffusivity in widespread white-matter areas including the corpus callosum, occipital, parietal, and frontal lobes in PSEN1 mutation carriers with SP. Volumetric measures were not different, and amyloid imaging showed low signal in sensorimotor cortex and other areas in a single subject with SP. Electrophysiological studies demonstrated both slowed motor and sensory conduction in the lower extremities in this same subject. Our results suggest that SP in carriers of the A431E PSEN1 mutation is a manifestation of widespread white-matter abnormalities not confined to the corticospinal tract that is at most indirectly related to the mutation's effect on amyloid precursor protein processing and amyloid deposition.

Episodic spastic paraparesis successfully treated with unaided blood transfusions: a case report.

BACKGROUND: Extramedullary haemopoiesis is a common compensatory phenomenon in most haemolytic anaemias. However, spinal cord compression due to extramedullary spinal epidural haemopoiesis is an extremely rare complication of thalassemia. In such situation patients present with paraplegia with a sensory level. Usual treatment options are surgery and/or radiotherapy. CASE PRESENTATION: Here we report a 27 year old Sri Lankan Muslim male with haemoglobin E-Beta thalassaemia presented with episodic spastic paraparesis when he was anaemic which was dramatically responded to blood transfusion therapy. CONCLUSION: Most of the reported cases with paraplegia have been treated with surgery with or without radiation therapy or radiation therapy alone. Our patient makes dramatic recovery after blood transfusion in each presentation.

Tau Accumulation in Primary Motor Cortex of Variant Alzheimer's Disease with Spastic Paraparesis.

We studied topographic distribution of tau and amyloid-ß in a patient with variant Alzheimer's disease with spastic paraparesis (VarAD) by comparing AD patients. The proband developed progressive memory impairment, dysarthria, and spastic paraparesis at age 23. Heterozygous missense mutation (L166P) was found in exon 6 of presenilin-1 gene. The proband showed prominently increased amyloid binding in striatum and cerebellum and asymmetrical tau binding in the primary sensorimotor cortex contralateral to the side more affected by spasticity. We suspect that upper motor neuron dysfunctions may be attributed to excessive abnormal tau accumulation rather than amyloid-ß in the primary motor cortex.

New spastic paraplegia phenotype associated to mutation of NFU1.

Recently an early onset lethal encephalopathy has been described in relation to mutations of NFU1, one of the genes involved in iron-sulfur cluster metabolism. We report a new NFU1 mutated patient presenting with a milder phenotype characterized by a later onset, a slowly progressive spastic paraparesis with relapsing-remitting episodes, mild cognitive impairment and a long survival. The early white matter abnormalities observed on MRI was combined with a mixed sensory-motor neuropathy in the third decade. Our case clearly suggests the importance of considering NFU1 mutation in slowly evolving leukoencephalopathy with high glycine concentration.

De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy.

KIF1A is a neuron-specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations in KIF1A were previously described in families with spastic paraparesis or sensory and autonomic neuropathy type-2. Here, we report 11 heterozygous de novo missense mutations (p.S58L, p.T99M, p.G102D, p.V144F, p.R167C, p.A202P, p.S215R, p.R216P, p.L249Q, p.E253K, and p.R316W) in KIF1A in 14 individuals, including two monozygotic twins. Two mutations (p.T99M and p.E253K) were recurrent, each being found in unrelated cases. All these de novo mutations are located in the motor domain (MD) of KIF1A. Structural modeling revealed that they alter conserved residues that are critical for the structure and function of the MD. Transfection studies suggested that at least five of these mutations affect the transport of the MD along axons. Individuals with de novo mutations in KIF1A display a phenotype characterized by cognitive impairment and variable presence of cerebellar atrophy, spastic paraparesis, optic nerve atrophy, peripheral neuropathy, and epilepsy. Our findings thus indicate that de novo missense mutations in the MD of KIF1A cause a phenotype that overlaps with, while being more severe, than that associated with recessive mutations in the same gene.

TECPR2: a new autophagy link for neurodegeneration.

Autophagy dysfunction has been implicated in a group of progressive neurodegenerative diseases, and has been reported to play a major role in the pathogenesis of these disorders. We have recently reported a recessive mutation in TECPR2, an autophagy-implicated WD repeat-containing protein, in five individuals with a novel form of monogenic hereditary spastic paraparesis (HSP). We found that diseased skin fibroblasts had a decreased accumulation of the autophagy-initiation protein MAP1LC3B/LC3B, and an attenuated delivery of both LC3B and the cargo-recruiting protein SQSTM1/p62 to the lysosome where they are subject to degradation. The discovered TECPR2 mutation reveals for the first time a role for aberrant autophagy in a major class of Mendelian neurodegenerative diseases, and suggests mechanisms by which impaired autophagy may impinge on a broader scope of neurodegeneration.

Early-onset cataracts, spastic paraparesis, and ataxia caused by a novel mitochondrial tRNAGlu (MT-TE) gene mutation causing severe complex I deficiency: a clinical, molecular, and neuropathologic study.

Mitochondrial respiratory chain disease is associated with a spectrum of clinical presentations and considerable genetic heterogeneity. Here we report molecular genetic and neuropathologic findings from an adult with an unusual manifestation of mitochondrial DNA disease. Clinical features included early-onset cataracts, ataxia, and progressive paraparesis, with sequencing revealing the presence of a novel de novo m.14685G>A mitochondrial tRNA(Glu) (MT-TE) gene mutation. Muscle biopsy showed that 13% and 34% of muscle fibers lacked cytochrome c oxidase activity and complex I subunit expression, respectively. Biochemical studies confirmed a marked decrease in complex I activity. Neuropathologic investigation revealed a large cystic lesion affecting the left putamen, caudate nucleus, and internal capsule, with evidence of marked microvacuolation, neuron loss, perivascular lacunae, and blood vessel mineralization. The internal capsule showed focal axonal loss, whereas brainstem and spinal cord showed descending anterograde degeneration in medullary pyramids and corticospinal tracts. In agreement with muscle biopsy findings, reduced complex I immunoreactivity was detected in the remaining neuronal populations, particularly in the basal ganglia and cerebellum, correlating with the neurologic dysfunction exhibited by the patient. This study emphasizes the importance of molecular genetic and postmortem neuropathologic analyses for furthering our understanding of underlying mechanisms of mitochondrial disorders.