Edward J. Fine

Sensorimotor gating in boys with Tourette's syndrome and ADHD: preliminary results.

Deficits in sensorimotor gating, defined by prepulse inhibition (PPI), have been associated with subcortical dopaminergic overactivity in animal and clinical studies. Utilizing supraorbital nerve electrical stimulation, we produced adequate blink responses and measured decreases in amplitude resulting from electric prestimuli just above sensory threshold. Seven boys comorbid for attention-deficit hyperactivity disorder (ADHD) and a tic disorder had significantly reduced PPI, compared to 14 screened controls and seven boys with ADHD alone. If independently replicated, these results may reflect greater neurologic immaturity in these comorbid subjects. Alternatively, these findings, together with other converging lines of evidence, suggest that deficient pallidal inhibition may be etiologically related to tic and movement disorders.

Stretch reflexes of triceps surae in normal man.

In order to learn more about stretch reflex behaviour of triceps surae, normal human subjects sat in a chair with one foot on a platform attached to a torque motor that produced phasic dorsiflexion displacements on the ankle. EMG activity was recorded from triceps surae and responses were obtained for various conditions. When the subjectss foot was relaxed, stretch of triceps surae produced a single EMG component at short-latency which increased in magnitude with increasing velocity of stretch. The response was not altered if the subject was asked to plantarflex or dorsiflex the ankle voluntarily when he felt the perturbation. It was reduced by vibration of the Achilles tendon. If the triceps surae was stretched while the subject plantarflexed his ankle, the short-latency response was followed by one and sometimes two long-latency responses. Like the short-latency reflex when the foot was relaxed, none of these responses was altered by the subjects planned movement after feeling the perturbation. All of the responses were suppressed to a similar degree by vibration. The long-latency reflexes depended on long-duration of stretching and relatively slow acceleration of stretch. The reflexes persisted after anaesthesia to the foot suggesting that muscle afferents were responsible. Interactions between H-reflexes and stretch-reflexes revealed that the afferent volley producing a stretch reflex acted like the afferent volley producing a small H-reflex. Responses at an interval of 30 ms to both an electrical stimulus for an H-reflex and a stretch stimulus were possible if the electrical stimulus produced only a small H-reflex and if the subject had been plantarflexing the ankle. The short-latency reflex when the foot was relaxed or exerting a background force appears to be the monosynaptic, Ia mediated stretch reflex. The physiological properties of the long latency reflexes are similar to those of the short-latency reflex, and they may represent, at least to a certain extent, response of the motor neuron pool to successive Ia bursts.

Neurophysiological study of subacute combined degeneration

Three patients with subacute combined degeneration of the spinal cord due to vitamin B12 deficiency showed a characteristic pattern of abnormalities on neurophysiological tests which corresponded to the clinical signs and symptoms. Peripheral nerve conduction studies showed an axonal degeneration peripheral neuropathy. Brain stem auditory evoked responses were normal; visual evoked responses were mildly abnormal and somatosensory evoked responses were moderately abnormal. These studies shed light on the pathology of this disorder and can aid in its diagnosis.

Disappearance of thalamic pain after parietal subcortical stroke

A hypertensive man had a long standing history of contumacious hyperpathia in the right upper extremity, resistant to medical therapy, secondary to a lacunar infarct in the left thalamus. A second cerebrovascular accident caused a small lesion in the left corona radiata, interrupting the thalamoparietal interconnections, and terminated the pain instantly. Interruption of the subcortical parietal white matter may more effectively control pain than cortical lesions. A few surgeons have successfully treated rebellious chronic pain with stereotaxic operations in the corona radiata, resulting in lesions very similar to our patients. This overlooked and nearly forgotten technique may still have value in treating selected cases.

Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.

Introduction: Of the nearly 38 million people in the USA who receive statin therapy, 0.1‐0.5% experience severe or life‐threatening myopathic side effects. Methods: We performed a genome‐wide association study (GWAS) in a group of patients with severe statin myopathy versus a statin‐tolerant group to identify genetic susceptibility loci. Results: Replication studies in independent groups of severe statin myopathy (n = 190) and statin‐tolerant controls (n = 130) resulted in the identification of three single‐nucleotide polymorphisms (SNPs), rs9342288, rs1337512, and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (P = 0.0003–0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina. Conclusion: Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle. Muscle Nerve, 2011

Orbital involvement as the initial manifestation of sarcoidosis: magnetic resonance imaging findings.

A 74‐year‐old man had diplopia, painful right ophthalmoplegia, proptosis, conjunctival injection, and facial skin lesions. Magnetic resonance imaging (MRI) revealed infiltration of the right intraorbital adipose tissue. Lesions were mixed low‐ and highsignal on T2‐weighted images and enhanced on fat‐suppressed T1‐weighted postcontrast images. A skin biopsy revealed numerous noncaseating granulomas consistent with sarcoidosis. Treatment with corticosteroids and chlorambucil led to a full clinical recovery. Sarcoidosis should be considered in the evaluation of orbital pseudotumor in elderly patients, even if no systemic manifestations of sarcoidosis are present

The Alice in Wonderland Syndrome

The Alice in Wonderland syndrome is a term applied to altered bizarre perceptions of size and shapes of a patients body and illusions of changes in the forms, dimensions, and motions of objects that a patient with this syndrome encounters. These metamorphopsias arise during complex partial seizures, migraine headaches, infections, and intoxications. The illusions and hallucinations resemble the strange phenomena that Alice experienced in Lewis Carrolls Alices Adventures in Wonderland. Charles Lutwidge Dodgson, whose nom de plume was Lewis Carroll, experienced metamorphopsias. He described them in the story that he wrote for Alice Liddell and her two sisters after he spun a tale about a long and strange dream that the fictional Alice had on a warm summer day. The author of this chapter suggests that Dodgson suffered from migraine headaches and used these experiences to weave an amusing tale for Alice Liddell. The chapter also discusses the neurology of mercury poisoning affecting the behavior of Mad Hatter character. The author suggests that the ever-somnolent Dormouse suffered from excessive daytime sleepiness due to obstructive sleep apnea.

The history of the blink reflex.

Most of Walker Overend’s seminal observations about the blink reflex remain unrefuted after 9 decades.’ In a succinct letter to the editor of Lancet in 1896, he reported that when the skin of the forehead is gently tapped with a stethoscope, the lower eyelid twitches on the same side, and slight tapping in the middle line of the forehead is followed by twitching in both eyelids. Overend further noted that the response has a motor pathway identical to that of the conjunctival reflex, and in severe cases of hemiplegia, the reflex is absent on the paralyzed side for a few days although the patient may close the eye perfectly. The reflex is not produced by communication of physical vibration. It is a true skin reflex and not a periosteal reaction.‘ This article recounts the life and work of Overend and contenders to the claim of priority for the discovery of the reflex. Their debates over priority and descriptions of the reflex are examined. The validity of Overend’s observations are judged by comparison with contemporary knowledge about the physiology of the reflex in normal and disease states. Walker Overend was born in Keighley, Yorkshire County, England, in 1858. Educated a t Skipton Grammar School, he won t h e Queen’s Scholarship to attend the Royal School of Mines in 1874.2 Four years later, he was awarded a scholarship to obtain a BSci a t the University of London, a n d in 1882 h e garnered t h e Brackenbury Scholarship at Balliol College in Oxford where he graduated with highest honors in physiology in 1886. He spent the following year on a Radcliffe Traveling Fellowship and studied the effects of curare and veratrine on striated muscle a t the Universities of Heidelberg and Strassbourg. After his return from the continent, he lectured in physiology a t St. George’s Hospital for 1 year, and in 1892 he published a textbook for medical students, The Elements of Human Physiology.2.3 Overend graduated with a BChir from Oxford in 1893 and formed a general practice with a classmate in Edmonton.2 In a letter to the editor published in Lancet on March 7, 1896, he described “a new cranial reflex.”’ The entire text is reproduced in figure 1. A pulmonary condition drove him from the smoky suburbs of London to the salubrious seaside town of Clacton-on-Sea. There he installed one of England’s first x-ray apparatuses in 1902. He became so enthralled with radiology that he gave up general practice in 1912 to devote himself entirely to this specialty.2 He developed an extensive consultation practice a t hospitals in the countryside east of London. In later years, he practiced with his son, Thomas.2 Overend’s portrait, almost forgotten, hangs in a corridor leading to the departm e n t h e once headed a t Royal E a s t Sussex Hospital in Hastings, England (figure 2). Overend correlated symptoms with radiographic a n d postmortem f indings i n h is book, T h e Radiology of the Chest.3 He made lasting contributions to a number of fields, including physiology, neurology, and radiology. He died on February 10, 1926, 2 years before the American publication of the second volume of his b o ~ k . ~ , ~ In 1901, Daniel Joseph McCarthy published an account of the supraorbital reflex without acknowledging Overend’s p r i ~ r i t y . ~ McCarthy, a Philadelphian, curiously published his observations in German, the title of which translates to English as “The supraorbital reflex. A new reflex in the territory of the 5th and 7 th cranial nerve pairs.” McCarthy elicited the supraorbital reflex by striking the skin overlying the nerve or the skin of the forehead up to the hairline with a percussion hammer. He also noted the bilateral response tha t Overend observed and that a tap on either side of the midline of the forehead usually elicited contraction of the orbicularis oculi. He substantiated Overend’s observation that facial paralysis eliminated the reflex and found that complete division of the supraorbital nerve for neuralga extinguished the reflex.5 General paresis abolished the reflex, while tabes dorsalis, in most cases, only diminished i t . 5 McCarthy did not examine t h e reflex in patients with hemiplegia or Parkinson’s disease. He concluded that supraorbital reflexes were “pure nerve reflexes” identical to tendon reflexes.5 Daniel McCarthy was born on June 22, 1874, in Philadelphia, Pennsylvania, where he received his

Association of intracranial meningioma with arteriovenous malformation

Simultaneous occurrence of a cerebral arteriovenous malformation and a primary brain tumor is rare. A case of a left occipital meningioma and a right parietotemporal arteriovenous malformation is reported. Clinical, radiological, and postmortem findings are described. Thirty previous reports of arteriovenous malformations associated with primary brain tumors are reviewed. In 18 cases the two lesions were intermixed or in close proximity. This spatial relationship between the lesions suggests more than a coincidental association. Several hypotheses are proposed to explain common causal connections.

Spatial disorientation and the Dyke-Davidoff-Masson syndrome.

A patient with Dyke-Davidoff-Masson Syndrome had a lifelong history of spatial disorientation and visual-spatial cognitive defects demonstrated by psychological tests. We suggest that the abnormalities of behavior and test performance may be related atrophic lesions demonstrated by pneumoencephalography and computerized axial tomography. We consider several explanations to account for the lack of compensation for these cognitive defects.