Spastic Gait Research Articles

Pure hereditary spastic paraplegia due to ade novomutation in theNIPA1gene

Hereditary spastic paraplegia (HSP) is a group of diseases with heterogeneous mode of inheritance and is characterized primarily by progressive spasticity of the lower limbs due to degeneration of long pyramidal tract. HSP type 6 (SPG6) is caused by mutations in the NIPA1 gene [1] (OMIM #600363) and accounts for less than 1% of autosomal dominant cases among Caucasians patients [2]. Traditionally, SPG6 was considered a pure (uncomplicated) form of HSP. Recent observations, however, expanded the phenotypic spectrum and linked NIPA1 mutations to some cases of more complex forms of HSP [3, 4]. We report here a family with a pure form of HSP due to a de novo transition mutation in the NIPA1 gene. The three affected members of the family were a 46 year-old parent and two children, aged 21 and 15 years of age. They all developed slowly progressive spastic gait that started during the first half of their second decade of life. Medical history was absent except for mild delayed speech development and attention deficit in the younger child and a single questionable generalized seizure in the older child that was not documented on electroencephalogram. This episode included a sudden loss of consciousness, lasted only few seconds and was associated with tongue biting and twitching of the left fingers but without clear postictal period. The proband, 36 years after symptom onset, had difficulty ambulating and was assisted by a walker. Both children had spastic gait but walked without assistance. Neurological examination of the affected family members was significant for marked spasticity, mild weakness of hip extensors, bilateral ankle clonus, globally hyperactive deep tendon reflexes that were more prominent in the lower extremities and extensor plantar responses. Cognition, ocular movements and cerebellar functions were all normal. Sequencing of the NIPA1 gene (Athena Diagnostics, Inc) revealed in all the affected family members a point mutation causing transition from adenine to guanine (G→A) at position 316. This mutation led to an amino acid change, from glycine to arginine, in codon 106. This specific mutation has been previously reported as pathogenic [3, 5] of a pure form of HSP, although cases of complicated HSP with epilepsy have been also documented [3]. Other ancillary tests included brain MRI studies, genetic testing for other autosomal dominant HSPs (SPG3A, SPG4 and SPG31) and extensive metabolic work-up were all normal. An MRI study of the proband’s thoracic spine showed spinal cord atrophy. Lack of symptoms or clinical signs in the parents of the proband led us to test them for a mutation in the NIPA1 gene (after they signed an informed consent for a research protocol approved by Columbia University IRB). The mutation was not present in the non-manifesting parents of the proband. True parenthood was confirmed using a panel of six highly informative unlinked microsatellite markers. To ensure specificity of this method, genetic polymorphism was also tested by three CEPH (1331-1, 1332-12, 1347-1) and showed perfect concordance. This finding supports the hypothesis that this was a de novo mutation. According to our knowledge, de novo mutations were never documented to cause SPG6 although such mutations were sparsely documented in other HSPs [6]. This finding strengths the assumption that this is a pathogenic mutation and emphasizes the need to consider autosomal dominant HSP even in the absence of family history.

The growth and the development of gastro-soleus contracture in cerebral palsy

Introduction: The development of contractures in children with spastic cerebral palsy is an important clinical as well as scientific issue. A common model for the development of contractures suggests that increased muscle tone shortens muscles, which leads to reduced growth of sarcomeres and tighter noncontractile muscle and tendon tissue. However, the spasticity is not the only factor influencing the contracture development. Based on our clinical observation we hypothesize that the body growth might play a key role in development of gastrocnemius contracture. Patients/materials and methods: We performed a retrospective cross-sectional analysis of 3D gait data of 244 children (385 legs) with spastic diplegic CP and equinus gait. Children were subdivided according to age into 6 subgroups (5–6, 7–8, 9–10, 11–12, 13–14 and 15–18 years) to show the changes during the whole period of growth. The height of all the participants at each visit was recorded. A formerly trained Generalized Dynamic Neuronal Network (GDNN) [1], a reliable method of automatic gait pattern recognition and classification, was used to discriminate between dynamic and fixed contracture of gastro-soleus muscle based on the ankle and knee kinematics and moments. The Spearman correlation coefficient was used to show the relationship between the growth and gastro-soleus contracture development. Results: The relative increase of fixed contracture of the gastrosoleus muscle between the age groups correlates positively with the relative increase in height (r=0.9; p<0.05). Therefore, the development of equinus contracture is tightly correlated with growth velocity in children with diplegic spastic CP. Discussion & conclusions: The range of ankle motion is decreasing during childhood [2]. It might sound contradictory but the spasticity of gastrosoleus muscle is decreasing between the ages 6–12 [3] as well. It seems that contracture development is not only moderated by spasticity and the reduction in tone does not prevent the development of contractures in CP [4]. We proved that the development of equinus contracture is tightly correlated with growth velocity in CP. Thereforewewould like to stress the growth spurt as an important period for contracture development as well as prevention.

Cervical spondylotic myelopathy with subacute combined degeneration

A 71-year-old man with spastic gait had exaggerated deep tendon reflexes, decreased vibration/position sensations, and positive Romberg sign. He had a history of total gastric resection and folate-deficient macrocytic normochromic anemia treated with vitamin B12, but had normal blood folate levels. Cervical T2-weighted magnetic resonance imaging (MRI) revealed reverse V-shaped posterior column hyperintensities (Fig. 1, Left, arrow) and C4–C5 intramedullary hyperintensities (Fig. 1, Right). He underwent C4–C5 laminoplasty for cervical spondylotic myelopathy complicated by subacute combined degeneration.

‘HIS WALKING ISN'T RIGHT DOCTOR’: A CASE OF HYDROCEPHALUS PRESENTING AS AN ABNORMAL GAIT

IntroductionHydrocephalus can present in a number of different ways in adult patients. Most typically these include headache and impaired cognition, or cranial nerve palsies. In this case a patient presented...

Diffusion tensor imaging in SPG11- and SPG4-linked hereditary spastic paraplegia

The aim of this study was to identify potential diagnostic markers of Hereditary Spastic Paraplegia (HSP). We investigated the white matter features of spastic gait (SPG)11- and SPG4-linked HSP, using diffusion tensor imaging performed with a 3-Tesla (3T) scanner. We examined four patients with SPG11 mutations, three with SPG4 mutations, and 26 healthy controls. We obtained maps of fractional anisotropy (FA) and mean diffusivity (MD), which we analyzed through both region of interest -based approach and tract-based spatial statistics (TBSS). Compared with healthy controls, SPG11 patients presented increased MD and decreased FA in the semioval centers, frontal and peritrigonal white matter, posterior limb of the internal capsule, and throughout the corpus callosum. Similar alterations were seen in the SPG4 patients at the levels of the semioval centers, the posterior limb of the internal capsule, the left cerebral pedicle, the genu and trunk of the corpus callosum, and the peritrigonal white matter on the left. No MD or FA alterations were observed in the cerebellar white matter. In a direct comparison, white matter alterations were more pronounced and widespread in HSP-SPG11 than in HSP-SPG4 patients. Joint TBSS analysis of all three groups confirmed significant widespread alterations of FA and MD values in the supratentorial white matter. This noninvasive study documented the presence of altered diffusivity in white matter in both forms of HSP, which could represent an important diagnostic marker of HSP. The association of reduced FA and increased MD in this patient population supports the interpretation of HPG as a neurodegenerative disorder.

Causes of Imbalance and Abnormal Gait That May Be Misdiagnosed

Disorders of gait and balance are common in medicine and often lead to referral for neurologic evaluation. Because the maintenance of balance and normal gait are mediated by complex neurologic pathways as well as musculoskeletal, metabolic, and behavioral considerations, the list of possible contributing causes is very large. Much of the time, the history and neurologic examination reveal the underlying cause or causes. There are instances, however, when there are limited neurologic findings, as well as no structural abnormalities on brain or spine magnetic resonance imaging studies to explain the imbalance or gait difficulty. In this article, selected disorders that may be overlooked in the neurologic examination and imaging studies are reviewed. Possible causes of imbalance include occult drug-induced ataxia, autoimmune ataxia, ataxia associated with tremor, bilateral vestibular hypofunction, and spastic or dystonic gait disorders with normal imaging.

Mobility After Traumatic Brain Injury

Reduced balance, spasticity, contractures, muscle weakness, and motor skill levels may all contribute to mobility limitations after traumatic brain injury (TBI), yet the key physical impairments that contribute to mobility limitations remain unclear. The aim of this study was to determine which physical impairments best predict mobility performance after a period of 6 months of rehabilitation. Participants with TBI were selected if they were receiving therapy for mobility limitations but were able to walk without physical assistance. The clinical assessment included measures of balance, spasticity, and contracture, and 3-dimensional quantitative gait analysis was used to quantify joint power generation and motor skill level on 31 adults with severe TBI. Mobility outcome was quantified with the high-level mobility assessment tool. Two variables, ankle joint power generation during the push-off phase of gait and motor skill level, explained 66.5% of the variability in mobility outcome. Balance, strength, and mobility performance, all improved significantly over the 6 months of rehabilitation. Only 2 participants had contractures, which affected mobility. Balance disorders were prevalent and improved with rehabilitation, yet they contributed to only a limited extent to the level of recovery in mobility. Ankle joint power generation at push-off was the strongest predictor of mobility outcome after 6 months of rehabilitation in ambulant people with TBI.

Livedo and ischemic strokes: diagnostic hints of a rare condition

Sneddon’s syndrome (SS) is a rare condition characterized by the combination of ischemic strokes and cutaneous livedo [1, 2], defined as the ‘‘persistent, not reversible with rewarming, violaceous, reticular or mottled pattern of the skin of trunk, arms or legs, consisting of regular unbroken circles (livedo reticularis) or irregular-broken circles (livedo racemosa)’’. Other well-defined neurological manifestations of SS include headache, seizures, and vascular dementia. Here, we report two cases with clinical and imaging features suggestive of SS. In both patients skin biopsy was performed and sections were stained with hematoxylin and eosin (HE general examination revealed diffused livedo racemosa (Fig. 1a). An extensive cardiological evaluation including an electrocardiogram, an echocardiogram and carotid ultrasound evaluation ruled out cardiovascular causes of stroke. Coagulation parameters (including fibrinogen and D-dimer), inflammatory indexes, syphilis serology, and autoimmune antibody panels including, ANA, ENA, ANCA, lupus anti-coagulants (LAC) and antiphospholipid antibodies (IgM and IgG anti-cardiolipin and anti-b2-microglobulin) were negative. A heterozygous mutation of factor V Leiden was detected. Brain MRI showed cortical atrophy and multiple ischemic lesions involving both the superficial and deep territories of posterior and middle cerebral artery (Fig. 1b). Skin biopsy showed intra-capillary and parietal widespread thrombosis (Fig. 1c). Oral anticoagulants and antipsychotic were added to therapy. A 65-year-old man (Case 2) presented with a 3-year history of progressive lower limbs weakness and mixed dysphagia. He had been having recurrent ischemic strokes since he was 55. He had history of myocardial infarcts, hypertension, and smoking. His neurological examination revealed dysphagia, ataxic and spastic gait, limbs hyperreflexia, right extensor plantar response. General examination revealed diffused livedo racemosa at the trunk and lower limbs (Fig. 1a). A cardiological evaluation and electrocardiogram ruled out the presence of heart arrhythmia; echocardiography demonstrated mild hypokinesia of apical and distal septum of lateral ventricle, as consequence of previous myocardial infarcts. Coagulation parameters and thrombophilic screening were normal. Brain MRI showed diffused cortical atrophy and multiple ischemic lesions (Fig. 1b) in both medium-sized superficial and deep, posterior and middle cerebral artery territories. Skin biopsy revealed intra-capillary and parietal widespread thrombosis (Fig. 1c). As for the first patient, oral anticoagulants were added to therapy. G. Cirillo A. Tessitore (&) F. Salemi S. Liguori S. Esposito G. Tedeschi Department of Neurology, Second University of Naples, 80138 Naples, Italy e-mail: alessandro.tessitore@unina2.it

Temporal motor coordination in the ankle joint following upper motor neuron lesions.

[Purpose] We compared ankle temporal motor coordination between stroke, spinal disease and healthy elderly groups, and investigated the relationship between motor impairments and gait speed. [Subjects] Twenty-four patients with stroke, 19 post-operative spinal disease patients and 17 healthy elderly subjects participated. [Methods] Ankle temporal motor coordination of the three groups was assessed using the simple reaction time, the foot-tapping test, and a rhythm task. Rhythm error and rhythm variation were analyzed using the results of the rhythm task. Isometric muscle strength, spasticity, muscle stiffness, somatosensory and 10-m gait speed of the stroke and spinal disease subjects were also measured. [Results] Only the stroke group showed significant reductions in temporal accuracy and consistency in the rhythm task. Simple reaction time and the rhythm task were significantly poorer in the stroke group, whereas the foot-tapping test was not. Stepwise multiple regression analysis indicated gait speed was explained by rhythm error and plantarflexor strength in the stroke group, and rhythm error and simple reaction time in the spinal disease group. [Conclusion] Poor performance in simple reaction time and the rhythm task in the stroke group suggest these tasks are controlled by the supraspinal central nervous system. Negative features, particularly motor coordination, are more associated with gait speed than positive features.

A novel experimental model of cervical spondylotic myelopathy (CSM) to facilitate translational research

Cervical spondylotic myelopathy (CSM) is the most common form of spinal cord impairment in adults. However critical gaps in our knowledge of the pathobiology of this disease have limited therapeutic advances. To facilitate progress in the field of regenerative medicine for CSM, we have developed a unique, clinically relevant model of CSM in rats. To model CSM, a piece of synthetic aromatic polyether, to promote local calcification, was implanted microsurgically under the C6 lamina in rats. We included a sham group in which the material was removed 30s after the implantation. MRI confirmed postero-anterior cervical spinal cord compression at the C6 level. Rats modeling CSM demonstrated insidious development of a broad-based, ataxic, spastic gait, forelimb weakness and sensory changes. No neurological deficits were noted in the sham group during the course of the study. Spasticity of the lower extremities was confirmed by a significantly greater H/M ratio in CSM rats in H reflex recordings compared to sham. Rats in the compression group experienced significant gray and white matter loss, astrogliosis, anterior horn cell loss and degeneration of the corticospinal tract. Moreover, chronic progressive posterior compression of the cervical spinal cord resulted in compromise of the spinal cord microvasculature, blood–spinal cord barrier disruption, inflammation and activation of apoptotic signaling pathways in neurons and oligodendrocytes. Finally, CSM rats were successfully subjected to decompressive surgery as confirmed by MRI. In summary, this novel rat CSM model reproduces the chronic and progressive nature of human CSM, produces neurological deficits and neuropathological features accurately mimicking the human condition, is MRI compatible and importantly, allows for surgical decompression.

Effect of botulinum toxin injection on length and lengthening velocity of rectus femoris during gait in hemiparetic patients

BackgroundIn hemiparetic patients, rectus femoris spasticity is one of the main causes of reduced knee flexion in swing phase, known as stiff knee gait. Botulinum toxin is often used to reduce rectus femoris spasticity and to increase knee flexion during swing phase. However, the mechanisms behind these improvements remain poorly understood. The aim of this study was (1) to quantify maximal rectus femoris length and lengthening velocity during gait in ten adult hemiparetic subjects with rectus femoris spasticity and stiff knee gait and to compare these parameters with those of ten healthy subjects and (2) to study the effect of botulinum toxin injection in the rectus femoris muscle on the same parameters. Methods10 patients with stiff knee gait and rectus femoris spasticity underwent 3D gait analysis before and one month after botulinum toxin injection of the rectus femoris (200U Botox®, Allergan Inc., Markham, Ontario, CANADA). Rectus femoris length and lengthening velocity were quantified using a musculoskeletal model (SIMM®, MusculoGraphics, Inc., Santa Rosa, California, USA). FindingsMaximal length and lengthening velocity of the rectus femoris were significantly reduced on the paretic side. There was a significant increase in muscle length as well as lengthening velocity during gait following botulinum toxin injection. InterpretationThis study showed that botulinum toxin injection in the spastic rectus femoris of hemiparetic patients improves muscle kinematics during gait. However maximal rectus femoris length did not reach normal values following injection, suggesting that other mechanisms are likely involved.

Adrenomyeloneuropathy Presenting With Adrenal Insufficiency

Adrenomyeloneuropathy (AMN), one of the variants of X-linked adrenoleukodystrophy (ALD), is inherited peroxisomal disorder associated with the accumulation of very long chain fatty acids (VLCFA). AMN is characterized primarily by involvements of long ascending and descending tracts of the spinal cord and peripheral neuropathy, which leads to spastic paraparesis and urinary and erectile dysfunction. We experienced the AMN case of a 33-year-old man presenting bilateral progressive spastic paraparesis, impotence and urge incontinence with primary adrenal failures, as confirmed by increased serum of VLCFA concentrations. Considering that somatosensory evoked potentials in posterior tibial nerve was the only abnormal finding in electrophysiologic findings when compared with the severe spastic gait pattern shown, it is necessary to follow up with electrophysiologic studies.

Adductor laryngeal breathing dystonia in NBIA treated with botulinum toxin-A

We report a rare case of neurodegeneration with brain iron accumulation (NBIA) presented with episodic inspiratory stridor. A 10-year-old boy presented with 3-year history of gradually progressive spastic gait and generalized dystonia (involving all four limbs, neck, jaw, and speech). MRI brain showed “Eye of Tiger” sign. He recently developed severe inspiratory stridor associated with almost gasping respiration. Direct video laryngoscopy showed paradoxical vocal cord closure during inspiration. He was treated with EMG-guided botulinum toxin-A injection given into bilateral thyroarytenoid muscles, resulting in dramatic response with complete disappearance of the stridor within a week. The effect lasted 18 months.

RELAPSING LYMPHADENITIS AND LOWER LIMB WEAKNESS; A DIAGNOSIS OF KIKUCHI-FUJIMOTO DISEASE

A 42-year-old female presented with a two-week history of difficulty walking, multiple falls and urinary hesitancy. Relevant past medical history included undiagnosed recurrent lymphadenopathy and immunogenic thrombocytopenic purpura. Several episodes...

Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy

Mutations in the spastic paraplegia 7 (SPG7) gene encoding paraplegin are responsible for autosomal recessive hereditary spasticity. We screened 135 unrelated index cases, selected in five different settings: SPG7-positive patients detected during SPG31 analysis using SPG31/SPG7 multiplex ligation-dependent probe amplification (n = 7); previously reported ambiguous SPG7 cases (n = 5); patients carefully selected on the basis of their phenotype (spasticity of the lower limbs with cerebellar signs and/or cerebellar atrophy on magnetic resonance imaging/computer tomography scan and/or optic neuropathy and without other signs) (n = 24); patients with hereditary spastic paraparesis referred consecutively from attending neurologists and the national reference centre in a diagnostic setting (n = 98); and the index case of a four-generation family with autosomal dominant optic neuropathy but no spasticity linked to the SPG7 locus. We identified two SPG7 mutations in 23/134 spastic patients, 21% of the patients selected according to phenotype but only 8% of those referred directly. Our results confirm the pathogenicity of Ala510Val, which was the most frequent mutation in our series (65%) and segregated at the homozygous state with spastic paraparesis in a large family with autosomal recessive inheritance. All SPG7-positive patients tested had optic neuropathy or abnormalities revealed by optical coherence tomography, indicating that abnormalities in optical coherence tomography could be a clinical biomarker for SPG7 testing. In addition, the presence of late-onset very slowly progressive spastic gait (median age 39 years, range 18-52 years) associated with cerebellar ataxia (39%) or cerebellar atrophy (47%) constitute, with abnormal optical coherence tomography, key features pointing towards SPG7-testing. Interestingly, three relatives of patients with heterozygote SPG7 mutations had cerebellar signs and atrophy, or peripheral neuropathy, but no spasticity of the lower limbs, suggesting that SPG7 mutations at the heterozygous state might predispose to late-onset neurodegenerative disorders, mimicking autosomal dominant inheritance. Finally, a novel missense SPG7 mutation at the heterozygous state (Asp411Ala) was identified as the cause of autosomal dominant optic neuropathy in a large family, indicating that some SPG7 mutations can occasionally be dominantly inherited and be an uncommon cause of isolated optic neuropathy. Altogether, these results emphasize the clinical variability associated with SPG7 mutations, ranging from optic neuropathy to spastic paraplegia, and support the view that SPG7 screening should be carried out in both conditions.

Central nervous system magnetic resonance imaging aspects of superficial siderosis

A 68-year-old man was evaluated with progressive gait difficulties, first noticed three years before. Neurological examination disclosed paraparetic spastic gait and lower limbs hyperreflexia with bilateral Babinski sign; mild left upper limb cerebellar ataxia; and left hearing loss. The magnetic resonance imaging (MRI) showed rims of hypointensity on T2 around the brainstem, cerebellum, and spinal cord, which was consistent with radiological diagnosis of superficial siderosis1 (Figs 1 to 3). There was no previous history of central nervous system (CNS) bleeding or trauma. Conventional angiographies were unremarkable. This rare case of primary superficial siderosis highlights the classic triad of hearing loss, ataxia, and myelopathy and its pathognomonic MRI findings2.

Progressive supranuclear palsy presenting as primary lateral sclerosis but lacking parkinsonism, gaze palsy, aphasia, or dementia

We report an autopsy case of progressive supranuclear palsy (PSP) that clinically showed only slowly progressive and symmetric upper motor neuron syndrome over a disease course of 12years. A female patient initially exhibited dysarthria at the age of 65, followed by gait disturbance and dysphagia. Neurological examination at age 67 disclosed pseudobulbar palsy, spastic gait, hyperreflexia, and presence of bilateral Hoffmann and Babinski signs. However, muscle atrophy, weakness, evidence of denervation on electromyography, vertical gaze palsy, parkinsonism, gait freezing, aphasia, speech apraxia, or dementia was not noted throughout the course. She was clinically diagnosed as having motor neuron disease consistent with so-called primary lateral sclerosis. Pathological examination disclosed histopathological features of PSP, including argyrophilic and tau-positive tufted astrocytes, neurofibrillary tangles, coiled bodies, and thread-like processes in the motor cortex and superior frontal gyrus, and to a lesser degree, in the basal ganglia and brain stem nuclei. In addition, severe fibrillary gliosis was noted in the precentral gyrus and corticospinal tract, being consistent with upper motor neuron syndrome observed in this case. No TAR-DNA binding protein 43-positive lesion, FUS pathology, Bunina body, or Lewy body-like hyaline inclusion was noted in the motor cortex or lower motor neurons. These findings suggest that when tau pathology is prominent in the motor cortex but is minimal in the basal ganglia and brain stem nuclei, a PSP case can lack all classic clinical features of PSP and show only slowly progressive upper motor syndrome, consistent with clinical picture of primary lateral sclerosis.

Tumors at the lateral portion of the C1–2 interlaminar space compressing the spinal cord by rotation of the atlantoaxial joint: new aspects of spinal cord compression

The authors describe 2 patients with C-2 nerve root tumors in whom the lesions were located bilaterally in the lateral portions of the C1-2 interlaminar space and compressed the spinal cord when the atlantoaxial joint was rotated. The patients were adult men with neurofibromatosis. Each presented with clumsiness of both hands and motor weakness of the extremities accompanied by spastic gait. Magnetic resonance imaging of the cervical spine performed with the neck in the neutral position showed tumors at the bilateral lateral portion of the C1-2 interlaminar space without direct compression of the spinal cord. The spinal cord exhibited an I-shaped deformity at the same level as the tumors in one case and a trapezoidal deformity at the same level as the tumors in the other case. Computed tomography myelography and MRI on rotation of the cervical spine revealed bilateral intracanal protrusion of the tumors compressing the spinal cord from the lateral side. The tumors were successfully excised and occipitocervical fusion was performed. The tumors were pushed out into the spinal canal from the bilateral lateral portion of the interlaminar spaces due to rotation of the atlantoaxial joint. This was caused by a combination of posteromedial displacement of the lateral mass on the rotational side of the atlas and narrowing of the lateral portion of the interlaminar space on the contralateral side due to the coupling motion of the lateral bending and extension of the atlas. The spinal cord underwent compression from both lateral sides in a one-way rotation. Without sustained spinal cord compression, intermittent long-term dynamic spinal cord compression from both lateral sides should induce a pathognomonic spinal cord deformity and the onset of paralysis. To the authors' knowledge, there have been no reports of the present conditions-that is, the bilateral protrusion of tumors from the bilateral lateral portion of the C1-2 interlaminar spaces into the spinal canal due to atlantoaxial rotation.

Unstable gait due to spasticity of the rectus femoris: Gait analysis and motor nerve block

We present the case of a 54 year-old man presenting with a right Brown-Séquard plus syndrome (BSPS) after a traumatic cervical spinal cord injury. After being operated on with selective tibial neurotomy and triceps surae lengthening because of a right spastic equinus foot, he developed a gait disorder at high speed. The patient complained about an instability of the right knee. Observational gait analysis exhibited an oscillating, flexion/extension motion of the right knee during stance, which was confirmed by gait analysis. Dynamic electromyographic recordings exhibited a clonus of the right rectus femoris (RF) during stance. The spastic activity of the RF and the abnormal knee motion totally reversed after a motor nerve block of the RF, as well as after botulinum toxin type A injection into the RF. We emphasize that complex, spastic gait disorders can benefit from a comprehensive assessment including gait analysis and nerve blocks.

Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings

Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD. We gathered clinical, biochemical, and molecular findings in 50 APBD patients with GBE deficiency from Israel, the United States, France, and the Netherlands. Brain and spine magnetic resonance images were reviewed in 44 patients. The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%). The median age was 51 years for the onset of neurogenic bladder symptoms, 63 years for wheelchair dependence, and 70 years for death. As the disease progressed, mild cognitive decline may have affected up to half of the patients. Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla. Atrophy of the medulla and spine was universal. p.Y329S was the most common GBE1 mutation, present as a single heterozygous (28%) or homozygous (48%) mutation. APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy.