A selective memory deficit caused by autoimmune encephalopathy associated with Hashimoto thyroiditis.

We report a longstanding selective memory deficit in a euthyroid 45-year-old woman who was being treated with levothyroxine for Hashimoto thyroiditis. The patient had complained of memory problems and deterioration of her concentration skills for about 2 years. Her endocrinologist thought that she was depressed. The patient's physical examination was normal. She scored a full 30 points on the Mini-Mental State Examination, but neuropsychological evaluation showed a significant deficit in her verbal memory. Routine blood tests and cerebrospinal fluid analysis showed only antithyroid peroxidase antibodies. Brain magnetic resonance imaging was normal. Electroencephalogram showed scarce intermittent bilateral multifocal theta waves. We increased the patient's daily dose of levothyroxine and started her on dexamethasone therapy. Five months later, we repeated the entire evaluation and found both her cognitive function and her electroencephalogram to be normal. Autoimmune encephalopathy associated with Hashimoto thyroiditis is already known to present with either stroke-like episodes or diffuse progressive deterioration. Our patient shows that the encephalopathy can present as a chronic selective memory deficit that can spare executive functions and short-term memory. This presentation can be missed or mistaken for depression, but can be diagnosed with a detailed neuropsychological evaluation.

Rapidly progressive dementia: causes found in a Greek tertiary referral center in Athens.

Dementia is generally considered as rapidly progressive [rapidly progressive dementia (RPD)], in cases with overt cognitive impairment, established within months. Data about the relative frequency of underlying diseases in cases of RPD are few and extremely variable, depending on the clinical setting. We examined the relative frequency of the underlying causes of RPD, in a university tertiary referral center, in Athens. A series of consecutive patients presenting with RPD in a 3-year period was included. All patients received a comprehensive clinical, imaging, and laboratory evaluation. Of a total of 279 patients hospitalized for dementia diagnosis, 68 patients had RPD (37 males and 31 females). Mean age at onset +/-SD was 65.5+/-10.0. The most common cause of RPD was secondary dementias, accounting for 18 cases (26.5%). Alzheimer disease and frontotemporal dementia were almost equally represented, accounting for 12 (17.6%) and 11 (16.2%) cases, respectively. Vascular dementia, Creutzfeldt-Jakob disease, and various neurodegenerative diseases accounted for 9 cases each (13.2%). In a tertiary referral center, secondary dementias represented the most frequent cause of cases presenting with RPD. As a substantial number of these cases are potentially treatable, our finding reconfirms and underscores the importance of an exhaustive evaluation in any case presenting with RPD.

Frequency and causes of early-onset dementia in a tertiary referral center in Athens.

OBJECTIVE: To investigate the frequency and causes of early-onset dementia (EOD) in consecutive patients in a highly specialized dementia referral center, focusing on unusual cases, particularly with early and/or rapid onset, in Athens, Greece. METHODS: Patients referred for dementia diagnosis according to specific referral criteria during a 3 years period. We examined the distribution of patients diagnosis and differences in sex, education, dementia severity, cognitive function, and the duration of disease (from onset to referral) between the EOD (<65 y) and the late-onset dementia (LOD) groups. RESULTS: From a total of 260 consecutive demented patients, there were 114 EOD patients or 44% of all demented patients. No significant differences were observed between the EOD and LOD groups in cognitive or behavioral measures. However, the duration from onset to consultation was significantly longer in the EOD group. Also, in the EOD group, the rates of patients with Alzheimer disease and Parkinson disease dementia were relatively low and the rate of patients with frontotemporal lobar degeneration was relatively high and the proportion of secondary dementias was high. CONCLUSIONS: We conclude that EOD patients are more likely to be seen in specialized settings. The underlying diseases are considerably different in EOD compared with LOD. Secondary causes are often found in patients with EOD. Patients with EOD had an unexpectedly longer time-to-diagnosis than patients with LOD. This argues for a need of better education about the clinical presentation of dementia in the young and middle aged.

Asymptomatic elevation of serum creatine kinase leading to the diagnosis of 4q35 facioscapulohumeral muscular dystrophy.

Persistent, asymptomatic (hyperCKemia) may be the prelude to, or the sole manifestation of, a neuromuscular disease. However, the clinical spectrum of facioscapulohumeral muscular dystrophy (FSHD) ranges from asymptomatic individuals with minimal clinical signs to patients who are wheelchair-bound. We describe a patient with persistent, asymptomatic hyperCKemia who received the diagnosis of 4q35 FSHD after a thorough stepwise investigation.

Age-related morphometric characteristics of human skeletal muscle in male subjects.

OBJECTIVE: The purpose of the present study is to investigate the age-related changes in muscle biopsies from the quadriceps femoris in male subjects of different ages. METHODS: A histological and histochemical study was performed on specimens from the quadriceps femoris from 8 males divided into two groups, under 50 and over 70 years of age. The following measurements were performed: a) number of type 1 and 2 fibres, b) diameter of type 1 and 2 fibres, c) percentage of the number and mean diameter of the two types in the interior and the peripheral area of fascicles. RESULTS: The proportion of type 2 fibres decreased significantly with age (p < 0.005), especially in the periphery of the fascicles, but the proportion of type 1 fibres was not significantly changed. The correlation of fibre size with age showed that type 2 fibres decrease in size with age. This finding was more evident in the periphery of the fascicles (p < 0.05). CONCLUSION: We found that type 2 skeletal muscle fibres decreased in size and proportion with increasing age. The existence of these age changes should be taken into account in the interpretation of muscle biopsies of aged individuals.

Low plasma total cholesterol in patients with Huntington's disease and first-degree relatives.

Recent studies indicate altered cholesterol homeostasis in Huntington's disease (HD) after it was found that cultured human and mice cells expressing mutant huntingtin show reduced mRNA of cholesterol biosynthetic enzymes. Plasma total cholesterol (TC) levels have been connected to degenerative disorders, but data for HD are lacking. We estimated plasma TC in three groups of HD related subjects: (a) patients with overt symptomatology, (b) subjects with expanded CAG repeat number in the Huntington gene before disease onset, and (c) siblings or descendants of HD patients, with normal CAG repeat number. Compared to TC levels of age-matched controls, all three groups had significantly lower plasma TC levels. The expected positive correlation of TC to age, present in the control group, was absent in the whole group or the three subgroups of the HD subjects. TC of the ApoE genotype subgroups showed small, non-significant differences. In the group of patients, TC levels were not related to severity of illness, duration of illness, and presence of depression or dementia in their symptomatology, while lower TC levels were found in patients with psychotic features. The results indicate altered cholesterol homeostasis in members of families with HD patients. Low TC levels have been connected to increased suicide risk in several studies, and high suicidal ideation has been reported in both HD gene carriers and non-carriers. Although low plasma TC levels do not necessarily imply alterations in brain cholesterol levels, a more detailed study of plasma lipids in HD patients and their first-degree relatives, as well as the search for genetic factors regarding cholesterol synthesis and disposition, are warranted.

Square-wave jerks and smooth pursuit impairment as subtle early signs of brain involvement in Langerhans' cell histiocytosis.

Central nervous system (CNS) involvement in Langerhans' cell histiocytosis (LCH) has been described as a progressive neurological disorder marked by motor and cognitive decline. Detailed analysis of ocular motor abnormalities is lacking. We report on a 60-year-old male with histologically confirmed LCH who developed oscillopsia and gait ataxia over a 1-year period. Eye movements recorded with infrared oculography revealed a high rate of square-wave jerks (SWJ) with frequencies of 41 min(-1) on average and amplitudes between 1 degrees and 7 degrees , as well as marked impairment of smooth tracking of sinusoidally moving targets. Furthermore, static posturography disclosed increased body sway, with an abnormally high sway path. The initial brain MRI was unremarkable. Due to the presumed cerebellar dysfunction we performed a second MRI 1 year later that disclosed deep cerebellar lesions compatible with LCH relapse within the CNS. The abnormal high SWJ rate and the impaired smooth pursuit performance correctly heralded later involvement of the cerebellum anticipating lesion appearance in the MRI.

Dementia as presenting symptom of primary hyperparathyroidism: favourable outcome after surgery.

The case of a 76-year-old female patient is presented with a two-year history of progressive dementia, apathy and gait impairment. Initially, Alzheimer's disease was diagnosed and she was given donepezil for one year with no significant improvement. An extensive blood and biochemical control revealed high serum calcium and parathormone levels, and normal thyroid hormones and anti-thyroid antibodies. Ultrasound of thyroid and parathyroid glands revealed an adenoma of the right parathyroid. The detailed investigation for causes of secondary hyperparathyroidism was negative. Due to the absence of clinical hyperparathyroidism she was initially treated conservatively. At referral, the neurological picture consisted of: mild signs of parkinsonism, moderate dementia (MMSE=15) and severe behavioural disturbances. Because of the continuous aggravation of the cognitive deficit, parathyroidectomy was decided although there were no clinical or laboratory signs of involvement from other organs. Three weeks after the operation the neurological picture showed dramatical improvement. Parkinsonism and behavioural disorders were remarkably reduced and the MMSE score raised to 25. In summary we report an exceptional case of primary hyperparathyroidism (PHPT) presenting as dementia and treated successfully by parathyroidectomy.

Spinal muscular atrophy: DNA fragmentation and immaturity of muscle fibers.

The presence of apoptotic fibers and the embryonic proteins desmin and vimentin were investigated in muscle biopsy specimens from patients with spinal muscular atrophy (SMA). Apoptosis was studied in 24 cases of SMA by means of in situ end labeling of nuclear DNA fragmentation using TUNEL staining and immunohistochemistry. Apoptotic nuclei were observed in 54.1% of the cases, and desmin and vimentin positive fibers were found in the majority of cases. A significant negative correlation was observed between the number of apoptotic nuclei and the duration of the disease, as well as between the number of desmin and vimentin positive fibers and the age of onset. These findings indicate that apoptosis, although probably a secondary phenomenon following denervation, plays a role in the progress of spinal muscular atrophy.

Orofacial dystonia related to Sjogren's syndrome.

Sjogren's syndrome (SS), either primary or secondary, is rarely accompanied by CNS complications. We report the exceptional case of a patient with secondary SS, who presented orofacial dystonia as a consequence of her disease. Initial treatment with clonazepam and levetiracetam was unsuccessful. However, dystonia was dramatically improved by a treatment with corticosteroids. This case demonstrates that corticosteroids can be efficacious in the treatment of dystonia related to SS.

Immunocytochemical study of cytoskeletal proteins in centronuclear myopathies.

The developmental status of muscle fibers was investigated in three cases of myotubular myopathy: one infant with the X-linked recessive form and two adult brothers with the autosomal, probably recessive, form of the disease. The presence of the developmentally regulated proteins desmin, vimentin and dystrophin was investigated by immunocytochemistry with the use of monoclonal antibodies. In the X-linked case, intense immunolabelling for vimentin and desmin was observed in the nuclear area of a great number of muscle fibers, while a few others showed sarcoplasmic dystrophin immunolabelling or were dystrophin-negative. In the adult cases, strong desmin immunoreactivity was observed, but only a few fibers labelled for vimentin. Dystrophin sarcolemmal immunolabelling was normal, but in some fibers dystrophin was observed in the area of the central nucleus. These findings are supportive of a maturational arrest of muscle fibers in the X-linked cases and possibly indicative of a similar mechanism in the adult form of centronuclear myopathy in these patients.

Morphological and morphometrical study of human muscle spindles in Werdnig-Hoffmann disease (infantile spinal muscular atrophy type I).

A study was made of the morphological and morphometrical features of muscle spindles in biopsies of patients with Werdnig-Hoffmann disease (infantile spinal muscular atrophy type I) to investigate the possible involvement of the muscle spindles in the pathological processes of the disease. A total of 57 muscle spindles from 26 cases were studied. The parameters determined were: the diameter and area of spindles, the number, diameter and area of intrafusal fibers, the number and area of nuclei. In addition, the ratio of the area of the intrafusal fibers to the area of nuclei and the ratio of the area of the spindle to the area of the intrafusal fibers were calculated. Statistical evaluation of the data showed significant differences regarding the area of the muscle spindle, the diameter of the intrafusal fibers and the mean area of nuclei of the intrafusal fibers, which were all smaller in patients than in controls (p=0.03, 0.01 and 0.02, respectively), while the thickness of the capsule was greater in patients than in controls (p=0.01). Our results indicate that the muscle spindle participates in the pathological processes of Werdnig-Hoffmann disease.

An Age-Related Morphometric Profile of Skeletal Muscle in Healthy Untrained Women.

There is a paucity of data on muscle biopsies in females of mixed ages in terms of age-related changes. Cross sections of autopsy material including the quadriceps femoris and biceps brachii muscles were obtained from 23 healthy women, aged 24-82 years, who had suffered sudden death. We calculated the percentage of the number, and the mean diameter, of type I and type II muscle fibers within the fascicles as well as in their peripheral parts. The number of type II fibers were shown to reduce significantly with age (p < 0.005), especially in the fascicle periphery, but the percentage of type 1 fibers did not alter significantly. It was noted that type II fibers diminished in size with age, indicating a relationship between fiber size and age. This result became more apparent in the fascicle periphery (p < 0.05). In women, type II muscle fibers were seen to reduce in size and number with advancing age. We postulate that regular physical activity can increase the size of type II muscle fibers, thus helping to both prevent and treat age-related muscle loss.

Symptomatic focal mononeuropathies in diabetic patients: increased or not?

The aim of this study was to investigate whether symptomatic mononeuropathies are more frequent in diabetic patients without symptoms of acute or subacute polyneuropathy than in the general population.For this purpose, six hundred and forty two consecutive outpatients with various acute symptomatic mononeuropathies (radial, ulnar or peroneal neuropathy, Bell's palsy or carpal tunnel syndrome) without symptoms of acute or subacute polyneuropathy were studied. The results showed that in 522 patients with symptomatic carpal tunnel syndrome (CTS) and in 38 patients with Bell's palsy, the rate of diabetes was 7.7% and 10.5%, respectively. These rates do not differ significantly from the anticipated frequency of diabetes in the general population. On the other hand, in 18 patients with radial neuropathy at (or distally to) the spiral groove, in 41 patients with ulnar neuropathy and in 23 patients with peroneal neuropathy at the fibular head, the respective rates were 27.8%, 12.2 % and 30.4%. These rates are significantly higher than those anticipated according to the frequency of diabetes in the general population. The findings of the present study indicate that only focal limb neuropathies due to acute external compression are more frequent in diabetic patients.

Friedreich's ataxia mimicking hereditary motor and sensory neuropathy.

Four patients from three unrelated families, with clinical and electrophysiological findings compatible with the diagnosis of hereditary motor and sensory neuropathy, are presented. The molecular analysis showed that the affected individuals were homozygous for the mutation in the X25 gene, characteristic of Friedreich's ataxia. These patients seem to represent a form of Friedreich's ataxia mimicking Charcot-Marie-Tooth disease.