Progressive limb-kinetic apraxia with myoclonus focal atrophy in the postcentral gyrus and the supplementary motor area]

We report a 70-year-old right handed man with a 5-year history of slowly progressive clumsiness of his left hand. A neurological examination disclosed mild rigidity and myoclonus in his left hand. He showed limb-kinetic apraxia, but neither ideational apraxia nor ideomotor apraxia was present. Aphasia and agnosia were also absent. He was thought to have the primary progressive limb-kinetic apraxia clinically. Brain CT and MRI revealed focal atrophy in the right postcentral gyrus and the supplementary motor area. A positron emission tomography (PET) study showed diffuse decrement of cerebral blood flow, predominantly in the right hemisphere. The decrease in the uptake of [18F]-Fluoro-deoxyglucose also revealed glucose hypo-metabolism, especially in the right frontal and parietal lobe. Striatal [11C]NMSP and [18F]FDOPA uptake were also reduced in an asymmetric pattern. These findings suggest that our patient is likely to have corticobasal degeneration. Transcranial magnetic stimulation using double pulse paradigm revealed a decrease in the level of cortico-cortical inhibition in the motor cortex on the affected side. Our results indicate increase in the excitability of motor cortical neurons in primary progressive limb-kinetic apraxia, likely due to a decreased excitability of cortico-cortical inhibitory mechanism as a result of focal degeneration of cortical neurons.     

Slowly progressive dressing and constructional apraxia: symptomatological study, especially for dressing apraxia]

In 1982, Mesulam drew attention to a clinical picture characterized by slowly progressive aphasia without dementia, and since then, there have been many such reports. Recently, there have been 30 reports of slowly progressive apraxia. However, the nature of this apraxia is not uniform. We now report a patient with slowly progressive dressing and constructional apraxia. The patient is a 60-year-old right-handed woman with a 2-year history of a slowly progressive praxic disturbance. On admission, she was alert and aware of this difficulty. A neurological examination disclosed mild rigidity and myoclonus in her left hand. A neuropsychological assessment disclosed severe dressing apraxia, which was unlikely to be caused by dementia and moderate constructional apraxia. Her dressing apraxia was manifested in upper limbs, neck, trunk and lower limbs. However, she could express verbally the action of dressing. She also showed mild limb-kinetic apraxia, but neither ideational apraxia nor ideomotor apraxia was present. Aphasia and agnosia were also absent. On an MRI, the bilateral cerebral hemispheres were atrophic (right > left). A 99m-Tc ECD SPECT revealed decreased uptake in the right cerebral hemisphere and left frontal lobe, and an EEG showed slow waves over the right cerebral hemisphere. There have been 30 reports of slowly progressive apraxia. Most of these cases presented with slowly progressive clumsiness in one or both hands as an initial symptom, followed by constructional, ideomotor or dressing apraxia. Our patient differed from these cases in that dressing and constructional apraxia progressed slowly without any other apraxia except only mild limb-kinetic apraxia. There was a similarity between dressing apraxia of our patient and that of Marie's and Brain's original cases.     

A case of motor neuron disease with dementia and apraxia of the upper limbs]

We report a 61-year-old, right-handed woman with motor neuron disease, dementia, and apraxia of the upper limbs. The patient developed clumsiness of the right hand and dysarthria two years and a half prior to admission. Neurological examination showed limb-kinetic apraxia and ideomotor apraxia, predominantly on the right side, in addition to dementia and anarthria. There was mild muscle wasting in the neck and hands. A muscle biopsy from the biceps muscle of arm as well as needle EMG revealed neurogenic changes compatible with motor neuron disease. Brain MRI indicated pyramidal tract degeneration. Three-dimensional brain perfusion imaging generated from SPECT demonstrated an asymmetric decrease in cerebral blood flow in the fronto-temporo-parietal regions, predominantly on the left side. This case suggests that asymmetric limb apraxia can be associated with motor neuron disease.     

Three-dimensional surface display with 123I-IMP in corticobasal degeneration]

A 65-year-old right-handed woman was admitted due to gait disturbance. She had suffered from progressive motor clumsiness in the left-sided limbs for four years. On admission, she was mildly demented, but not aphasic. Neurological examination disclosed constructional disability, limb-kinetic apraxia on the left side, and parkinsonism. Brain CT and MRI showed no responsible lesion. Three-dimensional surface display with 123I-IMP demonstrated decreased cerebral blood flow mainly in the right angular gyrus, and mildly in the right central region. She was clinically diagnosed as having corticobasal degeneration. Hypoperfusion in the angular gyrus and central region may account for constructional disability and limb-kinetic apraxia, respectively. Three-dimensional surface display with 123I-IMP appears to be useful for detecting the cortical region.     

Slowly progressive limb-kinetic apraxia with a decrease in unilateral cerebral blood flow

We report two patients with slowly progressive motor disorders, whose principal manifestations were asymmetric limb-kinetic apraxia and muscle rigidity. In both patients MRI revealed no responsible lesion, whereas single photon emission computed tomography (SPECT) showed a decrease in cerebral blood flow (CBF) in the unilateral hemisphere. One patient with mainly right-sided apraxia had a decreased CBF in the left central region between the frontal and parietal cortices, and the other patient with left-sided apraxia in the right parietal cortex. In agreement with asymmetric clinical symptoms, the regional CBF decrease in the unilateral cortical areas including the frontal and parietal cortices may suggest a degenerative disease, presumably diagnosed as having cortico-basal degeneration.     

Primary progressive limb-kinetic apraxia: a case report with an electrophysiological study]

We report a 53-year-old right handed woman with a 5-year history of slowly progressive clumsiness of her right hand. Neurologic symptoms was otherwise unremarkable except for mild dysarthria. Brain CT and MRI revealed a focal atrophic change in the left precentral gyrus. She was thought to have the primary progressive limb-kinetic apraxia. Electrophysiological studies were performed to explore physiologic mechanism of her apraxia. Surface EMG revealed co-contraction of antagonistic muscles in her right upper extremity with rhythmic myoclonic discharges. C-reflex was positive after median nerve stimulation only on the affected side. SEPs elicited by the median nerve stimulation were not enlarged and the SEP recovery curves showed no abnormal facilitation or inhibition. In addition, the premyoclonus spike was demonstrated by Jerk-locked averaging. Transcranial magnetic stimulation using double pulse paradigm revealed a decrease in the level of cortico-cortical inhibition on the motor cortex in the affected side. Median nerve stimulation given prior to the transcortical magnetic stimulation on the size of the magnetic evoked potential (MEP) revealed abnormal facilitations on the affected side, especially at conditioning-test interval of 60-80 ms. Therefore, our results indicate increase in the excitability of motor cortical neurons in primary progressive limb-kinetic apraxia, likely due to a decreased excitability of cortico-cortical inhibitory mechanism as a result of focal degeneration of cortical neurons.     

Slowly progressive apraxia: a MRI and positron tomography in 4 cases

Four right-handed patients (69, 58 and 68 year-old men; 85 year-old woman) complained of motor difficulties with their left hand (3 cases), or both hands predominant on the left side (1 case). Continuous (1 case) or intermittent (2 cases) myoclonus was noted in the left arm. These disorders gradually progressed for 3 to 10 years. Clinical examination disclosed absence of motor, sensory (except in 1 case), or visual deficit. There were no cerebellar signs, no parkinsonian features (except for mild rigidity in 1 case), and no oculomotor abnormality. On the other hand, neuropsychological examination showed evidence of visuo-constructive apraxia in all cases, dressing apraxia in 3/4 cases and writing impairment in 3/4 cases. There was no amnesia, no aphasia and no intellectual impairment. MRI showed atrophy of the parietal areas, predominant on the right side. A positron emission tomography study was performed in all cases, and twice in 1 case. Cortical energy metabolism was measured using either 18 F-fluorodeoxyglucose or 15 O-Oxygen, to calculate the cerebral metabolic rate of glucose (CMRglu) or oxygen (CMRO2) respectively. Cortical metabolism was significantly decreased in the whole cortex of the right hemisphere in 3 cases, and was also reduced in the cortex of the left hemisphere, significantly in 1/3 studied planes. Moreover, regional metabolic indices (CMRO2 or CMRglu/cortex) showed a significant decrease in both the right and left posterior associative areas (temporo-parieto-occipital cortex), predominantly marked on the right side in 3 cases, indicating bilateral cortical dysfunction. At follow-up, one patient became progressively demented, another had visuo-spatial disorders indicating a lesion of both parietal areas. The relationships of our cases with the slowly progressive apraxia syndrome and with corticobasal degeneration are discussed.     

Hand motor cortical area reorganization following cerebral infarction evaluated with functional MRI, near infrared spectroscopic imaging, and transcranial magnetic stimulation]

A 60-year-old, right-handed man suffered from left hemiparesis with upper limb dominance. CT and MRI revealed cerebral infarction of the entire right middle cerebral artery territory. His hemiparesis recovered excellently and residual neurological deficits 6 years later were left hand weakness(grasping power 9 kg vs. 35 kg in the right) and clumsiness. Functional MRI was performed. During right(normal) hand grasping, activation was seen in the left sensorimotor cortex and supplementary motor area. During left(paretic) hand grasping, activation was seen in the left (ipsilateral) sensorimotor cortex, right parietal cortex, and bilateral supplementary motor areas. Near infrared spectroscopic imaging showed similar results. During right hand grasping, left sensorimotor cortex was activated, and during left hand grasping, bilateral sensorimotor cortices were activated with ipsilateral predominance. Transcranial magnetic stimulation of the left motor hand area evoked right hand movement and stimulation of a point near that area evoked ipsilateral left hand muscle movement. Thus, the findings of the three techniques consistently suggest that the recovery of left hemiparesis of this patient was promoted by motor cortical area reorganization including the ipsilateral motor cortex.     

Infarct of the anterior limb of the right internal capsule causing left motor neglect: case report and cerebral blood flow study

A sixty-nine year old hypertensive man had left motor neglect following an infarct of the anterior limb of the right internal capsule. He also had left auditory extinction on verbal dichotic listening and a sligh constructional apraxia. Regional cerebral blood flow (CBF) was measured at rest with Xenon 133 inhalation and was found to be slightly decreased in a diffuse fashion. Motor activation of the right hand resulted in an increase of CBF in the contralateral superior rolandic area, whereas no such increase was found during motor activation of the left hand. This lack of cortical CBF increase on contralateral motor activation is interpreted as a consequence of the failure of some corticosubcortical connexions involved in motor arousal. The specifically dynamic appearance of regional CBF abnormalities, i.e. during selective activation as opposed to rest measurements, is consistent with the functional character of neglect.     

Progressive amusia and aprosody.

We report a case of slowly progressive amusia and aprosody in association with orofacial and eyelid apraxias. The patient was independent in daily living activities. Insight, judgment, and behavior were intact. Her language was normal, and she demonstrated no limb, dressing, or constructional apraxia. She had no prosopagnosia, no visuospatial disturbances, and no memory impairment. Imaging studies (computed tomography, magnetic resonance imaging, single photon emission computed tomography) indicated a selective disorder of the right frontal and temporal regions. Review of the literature shows an increasing number of reports of this degenerative syndrome affecting the left dominant hemisphere and language areas, whereas cases of the syndrome affecting the right hemisphere are rare. To our knowledge, this is the first case in which aprosody and amusia were associated with a focal cortical degeneration.     

A case of corticobasal degeneration presenting with visual hallucination]

We report a case of corticobasal degeneration (CBD) presenting with visual hallucination. A 65-year-old woman showed clumsiness of the left hand. Clinical symptoms slowly progressed to include rigidity, which was left side dominant, limb-kinetic apraxia of the left hand, disorder of construction and dressing, unilateral spatial neglect, cortical sensory loss and alien limb phenomenon. Cranial MRI showed atrophy of the parietal and medial aspect of the frontal lobes, which was more severe on the right than on the left. SPECT images showed hypoperfusion in the parietal, frontal and temporal lobes, which were similarly more severe on the right than on the left. We diagnosed the patient as having CBD based on the clinical symptoms. Two years' later, she developed recurrent visual hallucinations that were typically well formed and detailed. Since patients with CBD generally do not experience visual hallucination, this case is considered the very rare and indicates the possibility that visual hallucination may be one of the clinical symptoms of CBD.     

Symptomatology and Neuropathology of patients presenting with focal cortical signs

Here, we describe two patients who presented with focal cortical signs and underwent neuropathological examination. Case 1 was a 73-year-old woman with progressive speech disorder and abnormal behavior. She showed agraphia of the frontal lobe type, featured by the omission of kana letters when writing, other than pyramidal tract signs, pseudobulbar palsy, and frontal lobe dementia. Neuropathological examination, including TAR DNA-binding protein 43 (TDP-43) immunohistochemistry, revealed bilateral frontal and anterior temporal lobe lesions accentuated in the precentral gyrus and posterior part of the middle frontal gyrus. Both upper and lower motor neurons showed pathological changes compatible with amyotrophic lateral sclerosis. Case 2 was a 62-year-old man with progressive speech disorder and hand clumsiness. He had a motor speech disorder, compatible with apraxia of speech, and limb apraxia of the limb-kinetic and ideomotor type. Neuropathological examination revealed degeneration in the left frontal lobe, including the precentral gyrus, anterior temporal, and parietal lobe cortices. Moreover, numerous argyrophilic neuronal intracytoplasmic inclusions (Pick body) and ballooned neurons were observed in these lesions and the limbic system. The pathological diagnosis was Pick disease involving the peri-Rolandic area and parietal lobe. In these two cases, the distribution of neuropathological changes in the cerebral cortices correlated with the clinical symptoms observed.     

Visuo-constructional disorders and alexia-agraphia associated with posterior cortical atrophy

A 57 year-old woman developed a slowly progressive environmental agnosia and dressing apraxia without disturbances of language, memory, orientation and social activities. Two years later, alexia, agraphia, visual agnosia, constructional apraxia, simultagnosia and imitation apraxia of nonsymbolic gestures were also noted. Ophthalmic examination demonstrated a left inferior quadranopsia. Oral comprehension was normal. There was no loss of insight, and behavioral response was appropriately concerned. Computed tomography and magnetic resonance imaging revealed bilateral cortical atrophy in parieto-occipital areas, most pronounced on the right side, with enlargement of the ventricles. Positron emission tomography demonstrated low flow and metabolism values in the right parietal, temporal and occipital regions. This case is very similar to those of posterior cortical atrophy recently reported by Benson et al. (1988). It suggests a selectively degenerative dysfunction of posterior association cortex, sparing oral language and verbal memory.     

A case of antiphospholipid antibody syndrome with cerebral infarction showing slowly progressive pure motor monoparesis in unilateral upper extremity]

We reported a 68-year-old man with anti-phospholipid antibody syndrome who presented slowly progressive pure motor monoparesis(PMM) in left upper extremity as a sign of cerebral infarction. He had history of hypertension and hyperlipidemia. He first noticed clumsiness in left fingers, then weakness of left fingers with drop hand developing gradually in 2 to 6 weeks. He began to feel difficulty in raising left upper arm in 8 weeks and was admitted to our hospital. On admission, he exhibited severe weakness in distal portion and moderate weakness in proximal portion of left upper extremity. Deep tendon reflexes were slightly hyperactive in left side. Muscle strength of right upper extremity and bilateral lower extremities were normal. There was no sensory and autonomic abnormality. Laboratory examination revealed high titer of anti-cardiolipin IgM antibody. Brain MRI demonstrated a small cortical infarction in the right precentral gyrus. Cerebral angiography revealed severe stenosis in right common carotid artery. Other examinations including EMG were unremarkable. PMM in left upper extremity was considered to be caused by the ischemic lesion in the precentral motor cortex. Slowly progressive course might be explained by the hypovolemic factor due to the marked stenosis in right common carotid artery, poor collateral circulation, and abnormal coagulation caused by anti-phospholipid antibody syndrome.     

Alzheimer's disease presenting as corticobasal syndrome.

A 60-year-old man presented with slowly progressive left hemi-Parkinsonism, left hand apraxia, myoclonus, dystonia, visuospatial disturbances, and alien limb phenomenon, resembling corticobasal syndrome. Eight years later, neuropathology revealed features of Alzheimer's disease, with asymmetrical (right more than left) cortical tau burden with image analysis. The videotaped clinical features, neuropsychological aspects, and neuropathological correlates are presented and discussed.     

Apraxia in progressive nonfluent aphasia

The clinical and neuroanatomical correlates of specific apraxias in neurodegenerative disease are not well understood. Here we addressed this issue in progressive nonfluent aphasia (PNFA), a canonical subtype of frontotemporal lobar degeneration that has been consistently associated with apraxia of speech (AOS) and in some cases orofacial apraxia, limb apraxia and/or parkinsonism. Sixteen patients with PNFA according to current consensus criteria were studied. Three patients had a corticobasal syndrome (CBS) and two a progressive supranuclear palsy (PSP) syndrome. Speech, orofacial and limb praxis functions were assessed using the Apraxia Battery for Adults-2 and a voxel-based morphometry (VBM) analysis was conducted on brain MRI scans from the patient cohort in order to identify neuroanatomical correlates. All patients had AOS based on reduced diadochokinetic rate, 69% of cases had an abnormal orofacial apraxia score and 44% of cases (including the three CBS cases and one case with PSP) had an abnormal limb apraxia score. Severity of orofacial apraxia (but not AOS or limb apraxia) correlated with estimated clinical disease duration. The VBM analysis identified distinct neuroanatomical bases for each form of apraxia: the severity of AOS correlated with left posterior inferior frontal lobe atrophy; orofacial apraxia with left middle frontal, premotor and supplementary motor cortical atrophy; and limb apraxia with left inferior parietal lobe atrophy. Our findings show that apraxia of various kinds can be a clinical issue in PNFA and demonstrate that specific apraxias are clinically and anatomically dissociable within this population of patients.     

An autopsy case of frontotemporal lobar degeneration with the appearance of fused in sarcoma inclusions (basophilic inclusion body disease) clinically presenting corticobasal syndrome

We describe an autopsy case of basophilic inclusion body disease (BIBD), a subtype of frontotemporal lobar degeneration (FTLD) with the appearance of fused in sarcoma (FUS) inclusions (FTLD‐FUS), clinically presenting corticobasal syndrome (CBS). A 54‐year‐old man initially developed worsening of stuttering and right hand clumsiness. Neurological examinations revealed rigidity in the right upper and lower extremities, buccofacial apraxia, and right‐side dominant limb‐kinetic and ideomotor apraxia. Neuroimaging showed asymmetric left‐dominant brain atrophy and a cerebral blood flow reduction in the ipsilateral frontal region. At 56 years, his apraxia had advanced, and ideational apraxia was observed. Furthermore, the asymmetry in the limb‐kinetic and ideomotor apraxia had disappeared, and both conditions had become bilateral. He had a new onset of aphasia. His symptoms progressed and he died 9 years after the initial symptoms. The brain weighed 955 g. Diffuse brain atrophy was most obvious in the bilateral frontotemporal regions. The atrophy of the left superior frontal and precentral gyri and bilateral basal ganglia was remarkable. Histologically, there was a marked loss of neurons with gliosis in the affected areas, where basophilic neuronal cytoplasmic inclusions were observed. The inclusions were immunoreactive for FUS, p62, and TATA‐binding protein‐associated factor 15 (TAF15), but not for phosphorylated tau, transactive response DNA‐binding protein of 43 kDa (TDP‐43), neurofilament protein, or Ewing sarcoma (EWS). From these pathological findings, this case was diagnosed as having BIBD as an FTLD‐FUS variant. Spinal cord lower motor neurons were spared in number, similar to primary lateral sclerosis. Mutations in FUS were undetectable. Common background pathologies for CBS include corticobasal degeneration, Alzheimer's disease, PSP, FTLD with phosphorylated TDP‐43 inclusions (FTLD‐TDP), Pick's disease, Lewy body disease and CJD. However, FTLD‐FUS (BIBD) has been rarely reported. Our case suggested further pathological heterogeneity in CBS than had previously been reported. It is necessary to consider FTLD‐FUS (BIBD) as a background pathology for CBS in the future.     

Cerebellar symptoms in motor neuron diseases. Special form of amyotrophic lateral sclerosis plus syndrome

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive and selective loss of motor neurons in the cerebral cortex, brainstem, and spinal cord. The upper motor neuron syndrome is characterized by symptoms of spastic paresis. Muscle weakness and atrophy, fasciculations, and cramps are typical signs for the degeneration of the lower motor neurons. In 1994, the El Escorial criteria were proposed for the diagnosis of ALS. These criteria include ALS-plus syndromes, which are defined by an association of ALS with extrapyramidal features or dementia. In this paper, we present two cases of ALS associated with signs of cerebellar degeneration. According to the revised El Escorial criteria, the described unusual combination of upper and lower motor neuron signs in association with cerebellar ataxia can be classified as a specific form of ALS-plus syndromes.     

A case of corticobasal degeneration of which movemental disturbances were improved by administration of amantadine]

Corticobasal degeneration(CBD) is a neurodegenerative disorder characterised clinically by apraxia, cortical sensory loss, alien limb, dementia, oculomotor abnormalities, dysarthria, postural instability, akinesia, rigidity, and pyramidal signs. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. We reported a case of corticobasal degeneration of which praxic impairments were improved by administration of amantadine. The patient was a 63-year-old right-handed woman. She showed marked dysfunction including rigidity, limb kinetic apraxia, cortical sensory loss, ideomotor apraxia, and dressing apraxia. A brain MRI scan revealed bilateral cortical atrophy centered in the postcentral gyrus, more pronounced in the left hemisphere than the right. A SPECT scan showed a decrease in blood flow in the temporo-parieto-occipital regions, more pronounced in the left hemisphere than the right. An EEG showed a diffuse slowness. L-dopa had no effect on the symptoms of rigidity, limb kinetic apraxia, cortical sensory loss, ideomotor apraxia, and dressing apraxia. By administration of amantadine, rigidity and cortical sensory loss did not improve, but some praxic impairments, such as dressing apraxia and ideomotor apraxia, and the EEG improved. Upon withdrawal of amantadine, the improved symptoms deteriorated. Amitriptyline did not improve the deteriorated symptoms. After amantadine was re-administered, the same praxic impairments and the EEG improved again. This suggested that administration of amantadine had some effect on certain praxic impairments and the EEG.     

A case of motor disturbance in upper limb by parietal lesion; limb kinetic apraxia without visual compensation?]

We report a 75-year-old right-handed man who showed limbkinetic apraxia in the left hand caused by brain infarction of the right parietal lobe including postcentral gyrus. The hand shaping and posture preceding grasping was not appropriate, and clumsiness of the hand was not corrected by visual guidance. Fiber-tracking of the sensorimotor tract on diffusion tensor MRI and electrophysiological studies revealed that the lesion involved the area 1, 2, 5, and 7 of the cortices in Brodmann's nomenclature. In the most cases with limbkinetic apraxia caused by posterior lesion in the center region, hand clumsiness in manipulation should be corrected by visual guidance, which did not function in this case due to coexisting disturbances of kinesthesia with relatively large lesion in the parietal cortex.