Fahr’s syndrome presenting with pure and progressive presenile dementia

Abstract Fahr’s syndrome involves calcification of basal ganglia and dentate nuclei of the cerebellum. Clinically it may present with an array of movement disorders, dementia and other behavioural disturbances. Sporadic and familial cases have been reported with or without calcium/phosphorus metabolism. A rare form of frontotemporal dementia with neurofibrillary tangles and Fahr-type calcifications (DNTC) has been observed mainly in Japan. We report the singular case of a 50-year-old woman with progressive dementia but neither extrapyramidal symptoms nor a metabolic disorder. Brain CT showed Fahr-type calcifications in the basal ganglia, cerebellum and centrum semiovale as well as temporal atrophy; MRI showed diffuse atrophy predominantly in parietotemporal regions. The clinical and radiological features of our patient point to this uncommon form of dementia.     

Parkinsonian Syndrome Complicating Systemic Lupus Erythematosus

Two girls with florid extrapyramidal parkinsonism complicating systemic lupus erythematosus (SLE) are reported. One patient (15 years old) presented with extreme rigidity, irritability, and mutism initially diagnosed as acute psychosis. Examination revealed severe extrapyramidal akinetic mutism, along with marked restlessness. CT and MRI imaging of the brain were unremarkable. EEG revealed moderate generalized disturbance of background activity. ^99mTc-HmPAO SPECT cerebral scanning detected decreased regional cerebral blood flow at the basal ganglia. Dopamine-agonist drugs led to complete recovery after 3 months, along with normalization of EEG and SPECT alterations. The second patient (16 years old) was assessed for progressive bradykinesia and apathy impeding her active daily activities, and she was suspected to have developed depression. Neurologic assessment revealed a parkinsonian syndrome that was less severe than that of the first patient. The EEG showed mild disturbance of background activity, and ^99mTc-HmPAO SPECT demonstrated impaired regional cerebral blood flow over the basal ganglia. A parkinsonian extrapyramidal syndrome complicating SLE should therefore be taken into account in any patient with SLE presenting with marked behavioral alterations, rigidity, or akinetic mutism.     

A case of pseudohypoparathyroidism with intracerebral calcification

Intracerebral calcifications, especially in the basal ganglia, are observed in many kinds of diseases. A 41-year-old man is reported, who suffered from an acute epidural hematoma and underwent surgery to remove the hematoma. We detected very extensive intracerebral calcification on CT. Laboratory findings revealed hypocalcemia and hyperphosphatemia. General physical examination revealed characteristics typical of pseudohypoparathyroidism. The patient was diagnosed as having pseudohypoparathyroidism type I by the Ellsworth-Howard test. Since the advent of CT, the incidence of basal ganglia calcification has increased. CT is 5 to 15 times more sensitive than skull radiography in the detection of intracerebral calcification. Although many pathological states can cause basal ganglia calcification, most of the calcifications which are recognized on CT scans are physiological. But in cases in which basal ganglia calcifications are recognized also on plain radiographs, various kinds of symptoms including ones of basal ganglia origin are often recognized, and calcifications often extend to regions other than basal ganglia, eg. cerebellum, thalamus, etc. Pseudohypoparathyroidism is a rare disease which presents hypocalcemia, some characteristic physical appearances, and dementia. It is important to decide whether further examinations are necessary or not, when basal ganglia calcification is recognized incidentally on CT scan.     

A case of bilateral necrosis of the basal ganglia after hypotensive shocks

We reported a case with bilateral necrosis of the basal ganglia after hypotensive shocks. The patient was a 69-year-old woman, who fell into a hypotensive shock (B.P. below 40 mmHg) of unknown origin during examination of her bladder cancer and was admitted into CCU. After admission, hypotensive shocks were repeated four times (B.P. below 50 mmHg each time). Neurological examination revealed a left spastic hemiplegia. Brain CT on 10th day showed bilaterally low density areas around the basal ganglia and a diagnosis of brain infarction was made. She gradually presented quadriplegia and symptomatic changes from pyramidal to extrapyramidal signs. Brain CT on 24th day showed bilateral hemorrhagic infarction of the basal ganglia with enhanced effect. On 79th day, she again fell into shock and died. Neuropathological examination of the brain was as follows. 1) laminar necrosis of the deep layers of the cerebral cortex, 2) bilateral necrosis of the hippocampal Sommer sector, 3) bilateral necrosis of the caudate nucleus, putamen and pallidum with neuronal loss and infiltration of fat granule cells, 4) sparing of the internal capsules, 5) bilateral necrosis of the reticular zone of the substantia nigra, 6) foci of fresh necrosis and loss of Purkinje cells in the cerebellum. These lesions are consistent with those of selective vulnerability in hypoxia as described by Scholz et al. An extensive distribution of cerebral as well as basal ganglia necrosis in this case was caused by repeated shocks.(ABSTRACT TRUNCATED AT 250 WORDS)     

18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in propionic acidemia: clinical and MRI correlations.

The clinical data and the imaging findings of the positron emission tomography (PET) and the magnetic resonance imaging (MRI) studies in five patients, previously diagnosed to have propionic acidemia, were retrospectively reviewed. The patients were all normal at birth. The first clinical signs, typically hypotonia and failure to thrive, appeared during the first 2 years of life. With progression of the disease, the neurological findings consisted of variable degrees of dementia and extrapyramidal symptoms, notably dystonia, choreoathetosis and rigidity of variable degrees. Initial cerebral PET and MRI studies were normal. Follow-up MRI examinations showed progressive basal ganglia degeneration, with evidence of atrophy and signal abnormalities within the caudate nuclei and the putamina. The thalamic structures were normal. The PET studies demonstrated increased uptake in the basal ganglia and thalami, followed by decreased uptake in the basal ganglia at a later stage of the disease. The structural (MRI) and the functional (PET) studies of the brain were found to be complementary in the evaluation of propionic acidemia, and were in good correlation with the clinical findings.     

Extrapyramidal signs in Alzheimer's disease

The occurrence and type of extrapyramidal signs were investigated in 143 patients with dementia of the Alzheimer type. Only 8% of the patients were free of extrapyramidal signs. The most common type of extrapyramidal involvement was a rigid, hypokinetic, and hypomimic pattern. Resting tremor was rarely encountered. Dyskinetic signs, mostly orofacial, were seen in 17%. These observations suggest that in most patients with advanced Alzheimer's disease, there is a striatal dopaminergic hypofunction, appearing clinically as hypokinesia and rigidity. However, some patients exhibit predominantly dyskinetic signs, implying more complex basal ganglia dysfunction.     

Amyotrophic lateral sclerosis associated with extrapyramidal symptoms or signs]

This investigation was conducted to clarify the frequency and characteristics of ALS associated with extrapyramidal symptoms or signs in Wakayama prefecture. The questionnaires to survey ALS cases were mailed to all medical centers in Wakayama prefecture. A total of 252 cases were found to have motor neuron diseases. Among them, 204 cases fulfilled probable or definite according to El Escorial Criteria. In 10 of them, extrapyramidal signs were identified as follows: rigidity 50%, tremor 40% and akinesia 10%. Family history of ALS in these cases (20%) is higher than expected in usual ALS, and all of them are negative for SOD-1 mutation. Dementia and autonomic nervous symptoms were observed in several cases. Incidence of extrapyramidal signs in ALS resulted in 4.8%. The incidence of extrapyramidal signs is more frequent than expected by chance, suggesting that the degeneration of basal ganglia and/or substantia nigra may not be so rare in ALS.     

Paralytic ileus and atonic bladder in a case of mitochondrial encephalomyopathy--electrophysiological, chemical and pathological study with evidence of the peripheral nerve involvement

A 41-year-old female of mitochondrial myopathy characterized by recurrent paralytic ileus and atonic bladder with the evidence of peripheral nerve involvement was described. This patient was admitted to our hospital because of the episode of paralytic ileus and atonic bladder at the age of 40 and 41 (1987). She had noticed sporadic headache from 1967, constipation from 1977, tinnitus and hearing disturbance from 1984. One month after her second admission in 1987, her symptoms of paralytic ileus and atonic bladder gradually disappeared. She was then transferred to the department of neurology for the evaluation of underlining neurological disorders. Neurological examination revealed dementia, oro-lingual dyskinesia, and proximal muscular weakness. However, none of the following signs or symptoms were observed; Ophthalmoplegia, blepharoptosis, retinitis pigmentosa, myoclonus, cerebellar ataxia, sensory disturbance, and orthostatic hypotension. Deep tendon reflexes were normal. Planter responses were flexor. Pyruvate and lactate were elevated in both serum and cerebrospinal fluid. Brain CT scan displayed moderate cerebral atrophy and basal ganglia calcifications. EMG was normal except for the external anal sphincter muscles which showed a denervation pattern. Motor nerve conduction velocity was normal in the right median and the right peroneal nerves. Sensory nerve conduction velocity was also normal in the right median and the right sural nerves. However, the amplitude of sensory potential was low in both these nerves. Atonic type of neurogenic bladder was noted on cystometry. There was a lack of voiding desire. The number of active sweat glands iontophoretically stimulated by pilocarpine was reduced. The most prominent feature of the muscle biopsy (the left biceps brachii) was myopathic changes with ragged-red fibers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical correlations of CT scan-detected calcifications of the basal ganglia

A review of CT scans of 7,081 patients demonstrated calcifications of the basal ganglia in 53. The calcifications were evident in the skull roentgenograms of only 4 patients out of 40 in whom both CT scans and plain roentgenograms were available, demonstrating the superior resolution of this new method. Seventy-five percent of the patients were older than 50 years of age. Of the younger patients, 5 had had prior cranial irradiation; 1 had received cranial irradiation and intrathecal methotrexate therapy for meningeal leukemia; and 2 others had deep-seated arteriovenous malformations. Serum concentrations of calcium and phosphorus were normal in all 46 patients in whom they were measured. We conclude that the detection of small calcifications of the basal ganglia in persons above 50 years of age is infrequently associated with either clinical signs of basal ganglia dysfunction or calcium and phosphorus abnormalities. Calcium deposition in these patients may be related to vascular changes associated with aging. In younger patients a specific pathogenetic factor or underlying process is infrequently found.     

Gerstmann-Str?ussler-Scheinker disease with heterozygous codon change at prion protein codon 129]

A 53-year-old male was admitted to our hospital for progressive dementia and gait disturbance which had started at the age of 48. Examination indicated dementia, dysarthria, dysphagia, bilateral pyramidal signs, apraxia of the limbs, and extrapyramidal signs such as fine finger tremors, and rigidity of limbs. There were no cerebellar signs or myoclonus. His mother and elder brother showed similar symptoms and died at the ages of 53 and 50, respectively. EEG was normal. CT and MRI showed mild brain atrophy, but no cerebellar atrophy. T2 weighted image indicated low intensity areas covering bilateral caudate nuclei and putamina. A heterozygous amino acid change from methionine to valine was noted at codon 129 of the prion protein of the patient as well as in one of his son. The most likely diagnosis was Gerstmann-Str?ussler-Scheinker (GSS) disease without cerebellar atrophy. GSS may include a broad spectrum of brain pathology. Whether the codon change is associated with pathology without cerebellar atrophy is a problem that awaits further investigation.     

Two patients with pseudogout manifested by severe neck pain]

We reported 2 patients with pseudogout manifested by severe posterior neck pain. Patient 1 was a 78-year-old woman. She had experienced attacks of posterior neck pain several times for 4 years. On July 3, 2001, she developed severe pain in the posterior neck and left acromioclavicular joint, and was admitted to our hospital. On examination, her body temperature was 38.1 degrees C, ESR 140 mm/hr and CRP 14.7 mg/dl. Linear calcifications in meniscus of the right knee and left acromioclavicular joint were observed in roentgenograms. The CT of the cervical spines revealed multiple nodular calcifications in the ligamenta flava at the level of C3-C7. She was treated with NSAIDs, and her symptoms and inflammatory reactions rapidly subsided. Patient 2 was was a 76-year-old man. His clinical courses and laboratory findings were very similar to those of patient 1. Both patients presented here were older than 70, and shared such common clinical findings as back neck pain, fever, elevations of serum ESR and CRP level, and effiveness of NSAIDs. We could not detect any findings that could explain the neck pain and fever in cervical spinal roentgenograms and MRIs. Cerebrospinal fluid examinations showed no abnormalities. We diagnosed them as having cervical arthritis caused by calcium pyrophosphate dihydrate deposition (pseudogout) based on the cervical CT examinations, which showed multiple nodular calcifications in the ligamenta flava. Calcium pyrophosphate dihydrate deposition on cervical spine is very rare, and only 50 patients with this condition have been reported to date. In the literatures, the mean age of patients with cervical spine pseudogout is old (72.3 years old) and 84% of them are females. The ligamenta flava at the level of C3-C6 and transverse ligament of the atlas are most commonly involved. Pseudogout of the cervical spine should be considered as a differential diagnosis when we examine the elderly patients with back neck pain. Cervical spinal CT is the most sensitive and useful examination to diagnose this disease.     

A case of Nasu-Hakola's disease with T2-weighted MRI finding of reduced signal intensity in the thalamus and putamen]

A 30-year-old female received a head injury at the age of 22 years. Subsequently neurological and psychiatric symptoms, such as personality change, urinary incontinence, dementia and gait disturbance developed. On admission, her cognitive function was severely impaired. Brain CT disclosed cerebral atrophy, dilatation of the lateral ventricle and calcification of the basal ganglia. Pathologically membranous structures were recognized in bone marrow. On the basis of these clinical findings, a diagnosis of Nasu-Hakola's disease was made. In this case, a T2-weighted MRI finding of reduced signal intensity in the thalamus and putamen was characteristic. This finding may be related to intracranial calcification.     

Neuropsychological and 18FDG-PET studies in a family with idiopathic basal ganglia calcifications

Idiopathic basal ganglia calcification (FIBGC) is a rare autosomal dominant neurodegenerative disease, the main clinical signs of which are parkinsonism, cognitive deterioration and/or psychiatric troubles. Familial forms are rare. The underlying basis is not known. We performed detailed neurological, neuropsychological, brain CT scans and MRI evaluations in 15 patients of a large FIBGC family. Three patients also underwent a (18)FDG-PET scan study not previously performed in patients with FIBGC. Basal ganglia calcifications were present in 8 individuals, 3 of which had schizophrenia-like psychosis, cognitive and/or extrapyramidal signs. The mean age at disease onset was 34.0+/-3.6 years. Two patients had moderate executive dysfunction, whereas the proband had more severe dementia. (18)FDG uptake was significantly reduced in striatal or cortical areas, including the precuneus, posterior cingulate and superior temporal gyri. This study shows that calcifications and striatal neuronal degeneration can occur independently, and that functional changes in cortical areas can be observed early in FIBGC. Hypometabolism in the precuneus and posterior cingulate gyrus, which are involved in episodic memory processing, could be responsible for the episodic memory deficit found in the patients. Whether the underlying mechanism involves a neuronal loss or a functional alteration remains to be elucidated.     

Progressive dystonia following resuscitation from cardiac arrest

We report a case of a 55-year-old man in whom progressive extrapyramidal disease developed nearly 1 year after resuscitation from cardiopulmonary arrest. Parkinsonian features evolved within 3 months, and progressive generalized dystonia developed after 11 months. CT and MRI revealed bilateral basal ganglia infarction. Autopsy after 4 years of illness showed bilateral basal ganglia necrosis with preserved corticospinal tracts. These findings support earlier suggestions that postinfarction dystonia is mediated by a pyramidal system lacking normal striatal control.     

A case of idiopathic brain calcification associated with dyschromatosis symmetrica hereditaria, aplasia of dental root, and aortic valve sclerosis]

The patient was a 23-year-old woman. She was the product of a full-term pregnancy and normal delivery. At age 3, she was observed to have eruptions on the face and extremities. Gait disturbance and abnormal posture appeared when she was 17-year-old. Mental deterioration followed several years later, and these symptoms progressed gradually. On examination at age 23, mixture of hyperpigmented and hypopigmented macules were observed on the face and the dorsal aspects of the extremities. We diagnosed her skin lesion as dyschromatosis symmetrica hereditaria (DSH) based on dermatological findings, normal minimal erythema dose and normal unscheduled DNA synthesis of her skin fibroblasts. Neurologically, she showed moderate mental deterioration, dystonic posture, dystonic and spastic gait, and generalized hyperreflexia. Laboratory examinations, including parathyroid function, were normal. Brain CT scan revealed severe symmetrical calcifications in the basal ganglia, cerebral white matter, and dentate nucleus. She also showed aplasia of dental root and aortic valve sclerosis. Her father also revealed the same clinical features including skin lesion, movement disorder, mental deterioration, and severe aortic valve calcification. So we diagnosed this patient as familial idiopathic brain calcification associated with DSH, aplasia of dental root, and aortic valve sclerosis. Constellation of these clinical features does not match any previously established type of familial idiopathic brain calcification or hereditary dystonia. However, Patrizi et al reported a patient with DSH associated with torsion dystonia who was very similar to our patient. We propose that our patient and the patient reported by Patrizi et al construct a distinct clinical entity in familial idiopathic brain calcification or hereditary dystonia.     

Hereditary diffuse leukoencephalopathy with axonal spheroids caused by R782H mutation in CSF1R: case report

We report a biopsy-proven and genetically determined case with leukoencephalopathy showing autosomal dominant inheritance and pre-senile dementia. A 51-year old woman gradually developed a decline in cognitive functions with aphasia and epileptic seizures. Four of her family members were diagnosed as having dementia in their forties to sixties. Five years later she became apathetic and bed-ridden. Brain MRI initially showed fronto-temporal dominant cerebral atrophy with multiple small lacunar-like lesions in the deep white matter, but these white matter lesions became diffuse at an advanced stage. Such possibilities as hereditary vascular or fronto-temporal dementia were clinically suspected, but her family members requested a definitive diagnosis. Brain biopsy showed severe loss of myelin and axons in the white matter with relatively preserved cortical structure. The remaining axons disclosed irregular shapes with the formation of many spheroids, and these findings were consistent with a histopathological diagnosis of neuroaxonal dystrophy. DNA analysis disclosed a novel heterozygous c.2345G>A (p.782Arg>His) mutation in exon 18 of the colony stimulating factor 1 receptor gene (CSF1R). Hereditary diffuse leukoencephalopathy with axonal spheroids should be included in the differential diagnosis of familial occurrence of pre-senile dementia.     

An autopsy case of lymphomatosis cerebri showing pathological changes of intravascular large B‐cell lymphoma in visceral organs

We describe the case of a 61‐year‐old man presenting with subacute encephalopathy. The clinical manifestations included progressive dementia and pyramidal and extrapyramidal tract signs. Brain CT scan and MRI showed diffuse bilateral white matter changes in the cerebral hemispheres, basal ganglia, thalamus and brainstem. No contrast‐enhanced lesion was observed. Peripheral blood studies, CSF analysis, and brain and muscle biopsies were nonspecific and failed to reveal diagnostic evidence of any specific disease. The patient was diagnosed with and treated for a cerebral demyelinating disorder. Post mortem examination showed diffuse infiltration of lymphoma cells without mass lesions in the extensive cerebral white and gray matter with minimal intravascular patterns, particularly in the perivascular and periventricular spaces. These findings were consistent with lymphomatosis cerebri (LC). In other visceral organs such as the lungs, liver, kidneys and adrenal glands, blood vessels were plugged by numerous neoplastic cells which were morphologically and immunohistochemically similar to those observed in the CNS, consistent with intravascular malignant lymphoma (IVL). To our knowledge, this is the first autopsy report showing the coexistence of LC and IVL. This case suggests a possible link between LC and IVL.     

Familial idiopathic cerebral calcifications.

Nine members of a family spanning three generations showed bilateral calcifications of the basal ganglia with autosomal dominant inheritance. Two members developed chorea, dementia, and a characteristic speech disturbance (palialalia) in the third or fourth decade. A third member possibly shows the initial stage of a similar syndrome. Six members with calcifications but without neurological signs are younger than 25 years. All nine patients had normal calcium and phosphorus, and no evidence of endocrinological or somatic abnormalities. Thie 'isiopathic' picture must be differentiated from hypoparathyroidism and pseudohypoparathyroidism.     

Die Kufs-Erkrankung Seltene Ursache einer früh beginnenden Demenz

The case of a 35-year-old man with progressive dementia from the age of 17 is presented. Clinical examination showed mild extrapyramidal and cerebellar signs and rare myoclonus. Neuropsychological evaluation disclosed severe cognitive deficits. Magnetic resonance imaging (MRI) revealed moderate generalized atrophy with abnormal iron deposition in the basal ganglia. Positron emission tomography (PET) with 18-fluorodeoxyglucose (18-FDG) demonstrated clear temporoparietal hypometabolism. The clinical symptoms and course are typical for the rare adult type of neuronal ceroid lipofuscinoses (Kufs' disease). The diagnosis is supported by the electron microscope detection of an abnormal accumulation of lipid vacuoles and lipofuscin in the eccrine sweat glands and the rectal ganglia cells.     

Psychosis revealing familial idiopathic basal ganglia calcification

We describe the case of a 39-year-old woman presenting with auditory hallucinations and delusions responsive to antipsychotic drugs. Computerized tomography scans revealed basal ganglia calcifications in the proband and in her two asymptomatic parents. Extensive etiological clinicobiological assessment allowed us to exclude known causes of brain calcifications and diagnose familial idiopathic basal ganglia calcification (IBGC).