We report a 59 year old woman who presented with double vision, nuchal pain and mild dementia. On neurological examination she demonstrated third, sixth and seventh nerve palsies and ataxia. Following intravenous ACTH and oral prednisone therapy she showed a remarkable recovery which left her with only a left facial weakness. She remained well for two years. She then developed bulbar palsy and profound dementia. Pathological examination revealed progressive supranuclear palsy (PSP). This patient demonstrated a greater variability in the course of PSP than has previously been recognized.

Twocases,afather and son, of recurrent cerebellarataxiain the same family are reported, suggestingafamilial trait for the dysfunction. In the older male the onset of each episode (30-90 min.) was signalled by dysarthria which then progressed towards gait ataxia; the son presented closely similar clinical symptoms. Physical examination and blood chemistry revealed no obvious neurological deficit or biochemical abnormalities, with the exception of I-III and III-IV evoked auditory wave interpeak latencies, which were found markedly abnormal on the left side in the father but not in the son; the EEG of both individuals showed some diffuse, slow wave abnormalities. A low dose of acetazolamide, 250 mg daily, has successfully repressed recurrence of the attacks over the past six months. Temporary withdrawal for 14 days of the carbonic anhydrase inhibitor in the father coincided with two observed ataxic episodes.

Early Parkinson’s disease is taken to be the best human model of disordered basal ganglia function. An experimental study in Parkinsonians with swings in motor response to drug treatment suggests that general cognition is not controlled by dopamine mediated striatal activity. The variety of motor disorders in Parkinson’s disease cannot be explained by simple concepts. Although Parkinsonians cannot execute fast ballistic movements, an experimental study shows that they can adopt a predictive motor control strategy. It is argued that simple motor programs are not grossly disturbed in Parkinson’s disease. It is concluded that Parkinsonians cannot automatically execute learned motor plans.

Two patients with recurrent aseptic meningitis are reported. Intracranial epidermoid tumors were eventually found in both patients. CSF changes in our first case with an epidermoid tumor were similar to those reported in Mollaret’s meningitis, with an initial polymorphonuclear pleocytosis early in each attack, followed by a lymphocytic predominance several days later. Large cells which proved to be macrophages were also seen in the CSF of this patient. Both patients had meningitis attacks for several years before the underlying epidermoid tumor was found. Mollaret’s meningitis remains a diagnosis of exclusion. These patients should remain tumor suspects for many years and deserve careful and repeated investigation.

The amplitude and temporal modulation of the segmented EMG activity in flexor carpi radialis, evoked by imposed angular wrist extension, was studied with respect to the level of pre-existing background activity in rigid parkinsonian (PK) and dystonia musculorum deformans (DMD) patients. The interdependence of the evoked M1 and M2-3 segments on pre-existing background EMG activity and initial velocity of imposed displacement was established previously for a normal population. Individual responses of 21 parkinsonian and 12 dystonic patients were compared to the established normal “response volume”. The augmented magnitude of the M2-3 segment in rigid PK patients, which correlates to the measure of rigidity, could not be accounted for by the low level of pre-existing EMG activity. Therefore, increased descending facilitation does not impinge directly on alpha motoneurons. Paradoxical excitation in the shortened muscle and resetting of tonic tremor of the stretched muscle by the imposed wrist extension are two other demonstrated abnormalities which may also contribute to PK rigidity. In contrast, DMD patients demonstrated normal amplitude modulation of the M1 and M2-3 segments, but exhibited a disturbance of normal temporal mechanisms that result in constant duration of the M1 and M2-3 responses with imposed force step loads.

We evaluated the effects of acetazolamide in 4 young patients with Friedreich's ataxia by clinical and quantitative laboratory methods. Dynamic muscle function of the lower extremity was measured during isokinetic knee movements and gait. The acetazolamide trial was terminated at 7 to 11 weeks because of reported side effects or increased ataxia in 3 of the patients. The quantitative evaluations revealed lower dynamic strength values and alterations in the gait movement pattern in all patients. These changes, which were interpreted as deterioration, were partially reversible with cessation of acetazolamide. The advantages of such quantitative evaluations of dynamic muscle function in the evaluation of therapy in Friedreich's ataxia are discussed.

Free and total valproic acid (VPA) pharmacokinetic evaluation was carried out at steady state in six young epileptics who were also receiving other anticonvulsants. Subjects received their usual morning dose of VPA after an overnight fast. Blood samples for free and total VPA were taken prior to the dose and frequently thereafter for 12 hours. The calculated pharmacokinetic parameters for total VPA and free VPA were: half-lives of 7.5 ± 1.6 hours and 5.0 ± 1.5 hours, volumes of distribution of 0.189 ± 0.038 l/kg and 1.51 ± 0.98 l/kg, and clearances of 0.30 ± 0.06 and 3.6 ± 2.0 ml/min/kg., respectively. There was a strong correlation between percent free VPA and total VPA (r = 0.81) but marked inter- and intra-subject variations were seen. Studies attempting to correlate VPA levels to clinical response must take such data into account.

Forty patients with MS initially tested in our laboratory were recalled for repeat PSVEP testing approximately two years later. Twelve normal controls were tested in a similar manner approximately two years apart. The PSVEP positive peak latency changed little in the 24 control eyes (mean 1.4 msec, range 0-6) over the study interval. Most MS patient eyes also showed little change in PSVEP latency over the two year study interval. Fifty-eight eyes changed 8 msec or less. Eighteen eyes showed a PSVEP latency increase of 10 msec or more. Six of these eighteen eyes were symptomatic (attack of clinical optic neuritis), twelve asymptomatic during the study interval. Symptomatic eyes tended to have greater latency increases during the study interval than asymptomatic eyes.

Significant latency increases occurred with equal frequency in previously normal eyes (normal PSVEP on first test) and abnormal eyes (abnormal PSVEP on first test or previous clinical optic neuritis). Significant latency increases occurred with greater frequency in patients with a mixed or progressive course than in patients with a remitting-relapsing course, and in patients with greater disability ratings (Kurtzke 3-7) than in patients with lower disability ratings (Kurtzke 0-2). Bilateral latency increases occurred during the study interval more frequently than expected by chance. Patient age and disease duration did not significantly influence the number of PSVEP latency increases seen during the study interval.

Four eyes decreased in latency by 10 msec or more during the study interval. All these eyes had had an episode of acute optic neuritis which began in the 5 weeks immediately preceding the 1st PSVEP test.

In our MS patients, 13% of eyes per year developed latency increases of 10 msec or more. These may represent new demyelinating lesions. If so, one-third of these lesions were clincally symptomatic.

A clinical, electrophysiological and pathological review of 14 patients having oculoskeletal myopathy with abnormal mitochondria was undertaken. These patients present with ophthalmoplegia, and mild skeletal muscle weakness. The clinical course is slowly progressive. Electromyographic examination shows myopathic changes. Serum enzymes are normal. The diagnosis is confirmed by skeletal muscle biopsy which shows abnormal mitochondria, including crystalloid inclusions on electron microscopy. These patients form a distinct clinical group in which the risk of sudden cardiac death is much less than it is in the Kearns-Sayre syndrome.

Auditory brainstem responses (ABRs), visual and somatosensory evoked responses (VEPs and SEPs) and nerve conduction studies were conducted in 5 patients with abetaiipoproteinemia. The ABRs were normal in all cases. The VEPs were of normal amplitude but of increased latencies in two patients. The four eldest patients had delayed cortical SEPs but normal peripheral sensory nerve conduction studies. The peripheral motor conduction velocities were normal in all cases. The peripheral sensory studies showed normal velocity when a response was seen; however, the amplitude of the response was often reduced or it was absent. The electrophysiological studies reported here support a model of axonal loss of large myelinated fibres with secondary demyelination in abetaiipoproteinemia.

The segmented EMG activity in flexor carpi radialis to imposed wrist movements was studied in 18 hemiplegic subjects with vascular lesions of the sensorimotor cortex or internal capsule and compared to that in age-matched normal subjects. The segmented EMG activity in the stretched muscle was normalized against the maximum M response elicited by electrical stimulation of its peripheral nerve in hemiplegic and normal subjects. This M response was used to estimate the maximal activity of the motoneuron pool. Twelve of the hemiplegic patients showed a stereotyped abnormal segmentation pattern of the EMG activity characterized by: an increased M1 segment of prolonged duration with both an increased sensitivity to low initial velocities of displacement and an increased slope of the input-output relationship for the range of velocities tested; absent or diminished activity during the interval of the normal M2-3 segment; and a late component not evident in normal subjects. The increased magnitude of the EMG activity during the MI interval, markedly exceeded the normal range of control values. A method to demonstrate the response distribution of the interrelationship of the magnitude of the M1 segment using two variables (background EMG activity and initial velocity) for individual responses rather than average responses is presented. The results of the study indicate that: the increased excitability, reflected in the enhanced EMG over the M1 segment does not result from increased levels of resting alpha motoneuron activity and may result from disruption of polysynaptic internuncial influences on alpha motoneurons; the absent or diminished activity over the interval of the normal M2-3 segment may partially result from the interruption of a transcortical reflex by the vascular lesions.

Several authors have recently reported a neurological disorder associated with chronic vitamin E deficiency in man. Except in one patient, this deficiency has always been secondary to an underlying disease resulting in lipid malabsorption. We report a second case of such a neurological syndrome in a patient in whom vitamin E deficiency was an isolated finding.

The clinical picture in our patient was characterized by a diffuse muscle weakness most prominent distally and in the lower limbs, generalized areflexia, a decrease in proprioception and vibration sense and slight limb and gait ataxia. His condition improved on alpha tocopherol therapy so that it is very likely that vitamin E deficiency is responsible for his neurological deficit.

Since in our patient as well as in several other reported cases this condition has been treatable, it is important that this syndrome be recognized in children presenting a suggestive clinical picture even if they do not have lipid malabsorption.

Benign and malignant tumors of the choroid plexus in infancy are extremely uncommon. Diagnosis and management of a malignant tumor is described and the literature survey of the problem is presented.

From a review of the anatomical relationships and single unit activity in the components of the basal ganglia related to limb movement, it is concluded that the major outflow from basal ganglia circuits is via the motor cortex (area 4). Recent results of recording from area 4 neurons revealed that they preferentially “encode” the higher derivatives of movement, i.e. acceleration and jerk. In the parkinsonian (PK) patient and in the monkeys treated with l-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), EMG responses to imposed loads show a markedly increased gain of the “M2” component which depends upon the integrity of area 4 and which correlates with the severity of PK rigidity.

The above observations are considered, along with those of others (demonstrating prolonged movement times, a decreased “repertoire” of voluntary movements fractionation of voluntary movements’, inability in tracking movements without visual input, and failure to improve performance in PK’s) in relation to a model of the interactions between sensory input and motor programs. Using this model, it is hypothesized that the above PK movement deficits, as well as rigidity, can be accounted for by abnormal processing of the mechanoreceptor sensory input utilized in the generation and execution of movements. The MPTP treated monkey is suggested as a model in which to directly test the hypothesis.

Retrograde amnesia was assessed in demented and non-demented Parkinson’s patients using a test of remote memory spanning the years from 1920-1979. Results indicated that the demented patients 1) scored significantly below normal controls and 2) had equal impairment for all time periods. This pattern was like that seen in other dementing illnesses (i.e., Huntington’s and Alzheimer’s diseases), but different from that in amnesic disorders, such as Korsakoff s syndrome. The data, therefore, suggest qualitative differences in pattern of remote memory loss between the dementias and amnesic syndromes.

Aneurysmal bone cysts rarely affect the skull. Thirty-six cases including four reported in this paper are reviewed. The condition usually affects children and young adults and progresses rapidly. It may result in raised intracranial or intraorbital pressure. Complete excision of the mass is the treatment of choice, but if not feasible curettage followed by low dose radiotherapy is effective. As the prognosis in this condition is good, prompt diagnosis and early treatment are of utmost importance.

Cerebral aneurysms are extremely rare in all animals except man. We report the occurrence of a carotid-ophthalmic aneurysm in a cynomolgous monkey two months following accidental occlusion of the ipsilateral cervical internal carotid artery. This was documented angiographically. The aneurysm was deliberately ruptured by the insertion and withdrawal of fine needles. This produced a large subarachnoid hemorrhage visualized on CT scan. There was a progressive severe fall in cerebral blood flow and moderate vasospasm. The neurological status deteriorated on the tenth day and the animal was sacrificed on day 13. On electron microscopy, the aneurysm showed a fibrous wall, and the endothelium showed balloon-like endothelial cells with gaps. Corrugations occurred in the inner aspect of the anterior circulation arteries.

In the present paper we explore in some detail the hypothesis that the presence of familial aggregations in 10–15% of Parkinson’s disease cases is due in great part to the existence of well-defined familial subsets, rather than to chance occurrences. We describe the clinical and genetic characteristics of the two main subsets: “Essential tremor-related Parkinsonism” and the “Familial akineto-rigid Syndrome” previously identified.

The former type of Parkinsonism is associated at random, but with increased frequency, to an autosomal dominant disorder, usually essential tremor but occasionally OPCA. Two possible susceptibility factors were uncovered in this entity: an increased incidence of familial hyperthyroidism (augmentor factor) and a decreased incidence of the generally frequent HLA Haplotypes A1B8 or A2B5 (Protective factors).

The other presentation, the “familial akineto-rigid syndrome”, appears to be a definite disease entity with an autosomal recessive mode of inheritance (normal parents, increased incidence of identical parkinsonism in sibs, increased consanguinity rate in parents). This newly defined disorder deserves much further genetic and biochemical analysis.

A 22 year-old man died from multiple cerebral abscesses due to Petriellidium boydii 4 ½ months after an episode of near drowning. The autopsy showed dissemination to heart and kidney. This patient had no immunocompromising disease but was treated with corticosteroids. The treatment of this condition with ventricular shunting and amphotericin B is discussed and compared with the experience often other cases reported in the literature.

Six patients with Friedreich's ataxia, 4 males and 2 females, their ages ranging from 13 to 33 years, were studied. The early manifestations started between age 7 and 13 with an evolution time between 6 and 20 years. Serial visual and brain stem auditory evoked potential recordings were made. A progressive increase in latency, reduction in amplitude and in latency inter-ocular difference of PlOO were observed. The pattern of the reversal checker-board visual evoked potential was preserved. A disorganized BAEP pattern, a well defined potential I, a very small potential V and a delay in the interpeak latency were constant findings. The assumption is made of a progressive involvement of both visual and central auditory pathways. Pathophysiological mechanisms are discussed.