Yuen T. So

Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins

A molecular test for Alzheimers disease could lead to better treatment and therapies. We found 18 signaling proteins in blood plasma that can be used to classify blinded samples from Alzheimers and control subjects with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimers disease 2–6 years later. Biological analysis of the 18 proteins points to systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimers disease.

Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Objective: To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of autonomic and urologic disorders and low back and head pain. Methods: A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and the selected indications. Authors reviewed, abstracted, and classified articles based on the quality of the study (Class I–IV). Conclusions and recommendations were developed based on the highest level of evidence and put into current clinical context. Results: The highest quality literature available for the respective indications was as follows: axillary hyperhidrosis (two Class I studies); palmar hyperhidrosis (two Class II studies); drooling (four Class II studies); gustatory sweating (five Class III studies); neurogenic detrusor overactivity (two Class I studies); sphincter detrusor dyssynergia in spinal cord injury (two Class II studies); chronic low back pain (one Class II study); episodic migraine (two Class I and two Class II studies); chronic daily headache (four Class II studies); and chronic tension-type headache (two Class I studies). Recommendations: Botulinum neurotoxin (BoNT) should be offered as a treatment option for the treatment of axillary hyperhidrosis and detrusor overactivity (Level A), should be considered for palmar hyperhidrosis, drooling, and detrusor sphincter dyssynergia after spinal cord injury (Level B), and may be considered for gustatory sweating and low back pain (Level C). BoNT is probably ineffective in episodic migraine and chronic tension-type headache (Level B). There is presently no consistent or strong evidence to permit drawing conclusions on the efficacy of BoNT in chronic daily headache (mainly transformed migraine) (Level U). While clinicians’ practice may suggest stronger recommendations in some of these indications, evidence-based conclusions are limited by the availability of data.

Quantitative sensory testing Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Objective: This assessment evaluates the clinical utility, efficacy, and safety of quantitative sensory testing (QST). Methods: By searching MEDLINE, Current Contents, and their personal files, the authors identified 350 articles. Selected articles utilized computer operated threshold systems, manually operated threshold systems, and electrical threshold devices. The authors evaluated the use of normal values and the degree of reproducibility between the same and different systems. Articles were rated using a standard classification of evidence scheme. Results: Because of differences between systems, normal values from one system cannot be transposed to others. Reproducibility of results was also an important concern, and there is no consensus on how it should be defined. The authors identified no adequately powered class I studies demonstrating the effectiveness of QST in evaluating any particular disorder. A number of class II and III studies demonstrated that QST is probably or possibly useful in identifying small or large fiber sensory abnormalities in patients with diabetic neuropathy, small fiber neuropathies, uremic neuropathies, and demyelinating neuropathy. Conclusions: QST is a potentially useful tool for measuring sensory impairment for clinical and research studies. However, QST results should not be the sole criteria used to diagnose pathology. Because malingering and other nonorganic factors can influence the test results, QST is not currently useful for the purpose of resolving medicolegal matters. Well-designed studies comparing different QST devices and methodologies are needed and should include patients with abnormalities detected solely by QST.

Practice parameter for electrodiagnostic studies in carpal tunnel syndrome: Summary statement

Orthodromic SNAPs were recorded over the median nerve using needle electrodes at the wrist and elbow after stimulation of the thumb and middle fingers. CMAPs were recorded with concentric needle electrodes placed in the endplate zone of the APB after stimulation at the wrist and elbow. NCVs were determined for 28 male and 20 female normal subjects aged 16 to 62 years. There was no significant difference in NCV between male and female subjects. There was a decrease in NCV with increasing age. No CTS patients were studied. 186. Occupational Disease Surveillance. Carpal tunnel syndrome. MMWR Morb Mortal Wkly Rep 1989;38:485-489. Background Reference Source: Baker, 1990. 187. *Osborn JB, Newell KJ, Rudney JD, Stoltenberg JL. Carpal tunnel syndrome among Minnesota dental hygienists. J Dent Hyg 1990;64(2):79-85. Criteria Met (2/6: 1,2) Source: Medline Search. 188. Padua L, Lo Monaco M, Valente EM, Tonali PA. A useful electrophysiologic parameter for diagnosis of carpal tunnel syndrome. Muscle Nerve 1996;19:48-53. Criteria Met (6/6: 1,2,3,4,5,6). Source: Medline Search. Abstract: In 43 patients (50 hands) with clinical manifestations of mild-moderate CTS and 36 healthy volunteers (40 hands), orthodromic sensory nerve conduction velocity (SNCV) was measured with surface electrodes in the median nerve between the third digit and palm and between the palm and wrist. These figures were used to calculate the ratio of distal to proximal conduction (distoproximal ratio). All 90 hands were also subjected to other nerve conduction studies used for diagnosis of CTS. All control hands presented distoproximal ratios less than 1.0 reflecting higher conduction rates in the proximal segment. In contrast, 49 of 50 CTS hands (98%) presented reversed ratios (>1.0) indicating compromised proximal conduction. The sensitivity of this test was significantly greater than that of other methods evaluated, including comparative studies and segmental study of the palm-wrist portion of the median nerve. Segmental study of median SNCV with calculation of the distoproximal ratio is a sensitive technique for diagnosis of CTS in patients with normal findings in standard nerve conduction studies. Note: The author indicated by correspondence that the mean ± SD for the Control DML in Table 1 should read 3.2 ± 0.4 and not 3.2 ± 0.8 as published. 189. Padua L, LoMonaco M, Gregori B, Valente EM, Padua R, Tonali P. Neurophysiological classification and sensitivity in 500 carpal tunnel syndrome hands. Acta Neurol Scand 1997;96:211-217. Criteria Med (6/6: 1,2,3,4,5,6) Source: Medline Search. Abstract: Prospective study of 500 hands (379 patients) with clinical diagnosis of CTS symptoms. Normal values from the same laboratory previously published (Padua, 1996). In the 500 CTS patients, DML was prolonged (55%), median orthodromic sensory latency was prolonged (D2, 74%; D3, 67%). Of the remaining 117 patients with normal DML and median orthodromic sensory studies over 14 cm, the median sensory palmwrist NCV over 8 cm was abnormal in 21% and the distoproximo ratio of the median palm and digit segments was abnormal in 87%. 190. Palliyath SK, Holden L. Refractory studies in early detection of carpal tunnel syndrome. Electromyogr Clin Neurophysiol 1990;30:307-309. Criteria Met (5/6: 1,3,4,5,6) Source: Medline Search. Abstract: Using paired stimuli and varying the inter-stimulus interval, the absolute refractory period (ARP) and relative refractory period (RRP), were determined in 10 patients with mild electrophysiologic changes suggestive of CTS. They found that the sensory RRP was sensitive in diagnosing early CTS. 191. *Pavesi G, Olivieri MF, Misk A, Mancia D. Clinicalelectrophysiological correlations in the carpal tunnel syndrome. Ital J Neurol Sci 1986;7:93-96. Criteria Met (3/6: 2,3,5) Source: Medline Search. 192. Pease WS, Cannell CD, Johnson EW. Median to radial latency difference test in mild carpal tunnel syndrome. Muscle Nerve 1989;12:905-909. Criteria Met (4/6: 1,3,5,6) Source: Medline Search. Abstract: The following techniques were studied: (a) antidromic DSL median radial differences to the thumb, (b) antidromic DSL after stimulation at the wrist and recording from the third digit, (c) median mid-palmar DSL compared as a ratio of the wrist to middle finger DSL, (d) median ulnar DSL latency difference between the ulnar Practice Parameter: Carpal Tunnel Syndrome Muscle & Nerve Supplement X 2002 S971 SNAP recorded from the little finger after stimulation at the wrist and the median DSL after stimulation at the wrist and recording from the middle finger, and (e) median motor DML after recording from the APB after stimulation at the wrist. Three hundred thirty-three symptomatic hands in 262 patients were initially evaluated with subgroups of patients with CTS evaluated with different tests. The median radial DSL difference and median ulnar DSL difference were most likely to be abnormal followed by median DSL then the palmto-wrist DSL latency ratio and lastly the DML. 193. Pease WS, Cunningham ML, Walsh WE, Johnson EW. Determining neurapraxia in carpal tunnel syndrome. Am J Phys Med Rehabil 1988;67:117-119. Criteria Met (5/6: 1,3,4,5,6) Source: Medline Search. Abstract: With needle stimulation at the wrist and midpalm, CMAPs were recorded over the APB in 25 CTS patients and 23 healthy asymptomatic persons. They found a significant difference in the amplitude of the CMAP in the CTS group when compared to the control group. They propose that this is evidence for conduction block (neurapraxia) in CTS. 194. Pease WS, Lee HH, Johnson EW. Forearm median nerve conduction velocity in carpal tunnel syndrome. Electromyogr Clin Neurophysiol 1990;30:299-302. Criteria Met (4/6: 1,3,4,5) Source: Medline Search. Abstract: The NCV of the median nerve in the forearm was determined by 2 methods: (a) stimulation in the forearm and recording the nerve action potential at the wrist, and (b) stimulation at the wrist and elbow with recording over the APB, in 21 CTS patients and 16 control subjects. They found that the forearm NCV was slowed in the CTS group using either technique. The authors have proposed that this suggest that there is proximal nerve dysfunction as a result of median nerve compression in the carpal tunnel. 195. *Peterson GW, Will AD. Newer electrodiagnostic techniques in peripheral nerve injuries. Orthop Clin North Am 1988;19:13-25. Criteria Met (0/6) Source: Narkis, 1990. 196. *Phalen GS. The carpal tunnel syndrome: clinical evaluation of 598 hands. Clin Orthop 1972;83:29-40. Background Reference. Source: Katz 1990 (J Rheumatology). 197. *Phalen GS. The carpal tunnel syndrome: seventeen years’ experience in diagnosis and treatment of 654 hands. J Bone Joint Surg 1966;48:211-228. Criteria Met (1/6: 2) Source: Meyers, 1989. 198. Phalen GS, Gardner WJ, LaLonde AA. Neuropathy of the median nerve due to compression beneath the transverse carpal ligament. J Bone Joint Surg 1950;32-A:109-112. Background Reference. Source: Braun, 1989. 199. Plaja J. Comparative value of different electrodiagnostic methods in carpal tunnel syndrome. Scan J Rehabil Med 1971;3:101-108. Criteria Met (4/6: 1,3,5,6) Source: Joynt, 1989. Abstract: The following techniques were studied: (a) CMAP potentials were recorded after stimulation at the wrist and recording with coaxial needle electrodes, (b) orthodromic SNAPs with stimulation over the index finger and recording with surface electrodes at the wrist, (c) needle EMG using a coaxial needle, (d) strength/duration curves and chronaxy. Fifty-six cases of CTS and 20 normal subjects were evaluated. Sensory latencies were more likely to be abnormal than the other techniques measured. 200. Preston DC, Logigian EL. Lumbrical and interossei recording in carpal tunnel syndrome [see comments]. Muscle Nerve 1992; 15: 1253-1257. Criteria Met (5/6: 1,3,4,5,6) Source: Medline Search. Abstract: Median motor studies are commonly “normal” in mild carpal tunnel syndrome (CTS). This reflects either the sparing of motor compared to sensory fibers, or the inability of conventional studies to detect an abnormality. A novel approach to demonstrate early motor fiber involvement in CTS is the placement of the same active electrode lateral to the third metacarpal, allowing recording from the second lumbrical or the deeper interossei, when stimulating the median or ulnar nerves at the wrist, respectively. We compared the difference between these latencies in 51 normal control hands to 107 consecutive patient hands referred with symptoms and signs suggestive of CTS, who were subsequently proven to have electrophysiologic CTS by standard nerve conduction criteria. A prolonged lumbrical-interossei latency difference (>0.4 ms) was found to be a sensitive indicator of CTS in all patient groups. It was also helpful in patients with coexistent polyneuropathy, where localization of median nerve pathology at the wrist was otherwise difficult. 201. *Preston DC, Ross MH, Kothari MJ, Plotkin GM, Venkatesh S, Logigian EL. The median-ulnar latency difference studies are comparable in mild carpal tunnel syndrome. Muscle Nerve 1994; 17: 1469-1471. Criteria Met (2/6: 1,3). Source: Medline Search. Abstract: Compares sensitivity 159 patients of orthodromic palm-wrist mixed palmar median-ulnar peak latency difference with normal <0.4 ms, antidromic wrist-D4 sensory median-ulnar onset latency difference with normal <0.5 ms, and the second lumbrical/interossei motor with normal <0.5 ms. See discussion of benefits of techniques and diagrams of electrode placements and line drawings of electrode and stimulator placement. 202. Preswick G. The effect of stimulus intensity in motor latency in carpal tunnel syndrome. J Neurol Neurosurg Psychiatry 1963;26:398-401. Criteria Met (4/6: 1,3,5,6) Source: Loong, 1971. Abstract: With stimulation at the wrist and coaxial needle electrode recording from the APB, DMLs were recorded at super-maximal stimulation and threshold stimulation in 29 CTS hands f

Assessment: Botulinum neurotoxin for the treatment of spasticity (an evidence-based review) Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Objective:To perform an evidence-based review of the safety and efficacy of botulinum neurotoxin (BoNT) in the treatment of adult and childhood spasticity. Methods:A literature search was performed including MEDLINE and Current Contents for therapeutic articles relevant to BoNT and spasticity. Authors reviewed, abstracted, and classified articles based on American Academy of Neurology criteria (Class I–IV). Results:The highest quality literature available for the respective indications was as follows: adult spasticity (14 Class I studies); spastic equinus and adductor spasticity in pediatric cerebral palsy (six Class I studies). Recommendations:Botulinum neurotoxin should be offered as a treatment option for the treatment of spasticity in adults and children (Level A). GLOSSARYBoNT = botulinum neurotoxin; CP = cerebral palsy; FDA = Food and Drug Administration; SNAP = synaptosomal-associated protein; VAMP = vesicle-associated membrane protein.

Lamotrigine for HIV-associated painful sensory neuropathies: A placebo-controlled trial

Objective: To evaluate the efficacy and tolerability of lamotrigine (LTG) for the treatment of pain in HIV-associated sensory neuropathies. Methods: In a randomized, double-blind study, patients with HIV-associated distal sensory polyneuropathy (DSP) received LTG or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase. Randomization was stratified according to whether or not patients were currently using neurotoxic antiretroviral therapy (ART). Results: The number of patients randomized was 92 (62 LTG, 30 placebo) in the stratum receiving neurotoxic ART and 135 (88 LTG, 47 placebo) in the stratum not receiving neurotoxic ART. Mean change from baseline in Gracely Pain Scale score for average pain was not different between LTG and placebo at the end of the maintenance phase in either stratum, but the slope of the change in Gracely Pain Scale score for average pain reflected greater improvement with LTG than with placebo in the stratum receiving neurotoxic ART (p = 0.004), as did the mean change from baseline scores on the Visual Analogue Scale for Pain Intensity and the McGill Pain Assessment Scale and patient and clinician ratings of global impression of change in pain (p ≤ 0.02). The incidence of adverse events, including rash, was similar between LTG and placebo. Conclusions: Lamotrigine was well-tolerated and effective for HIV-associated neuropathic pain in patients receiving neurotoxic antiretroviral therapy. Additional research is warranted to understand the differing response among patients receiving neurotoxic antiretroviral therapy compared with those not receiving neurotoxic antiretroviral therapy.

Evaluation of thermography in the diagnosis of selected entrapment neuropathies

We studied 20 normal subjects, 22 patients with carpal tunnel syndrome, and 15 with ulnar neuropathy at the elbow to compare the diagnostic accuracy of infrared thermography with that of conventional electrodiagnostic studies. We found abnormal thermograms in 55% of patients with carpal tunnel syndrome and 47% with ulnar neuropathy, using 2.5 SD from the normal mean as criteria for abnormality. The abnormalities consisted of either an increase in interside temperature difference in the fingers and hands or an alteration of the normal thenar-hypothenar temperature gradient in the fingers. The sensitivity of thermography was considerably lower than that of conventional electrodiagnostic methods. Moreover, the thermographic abnormalities were nonspecific, and could be misleading as they did not reliably identify the side of lesion or distinguish between median or ulnar nerve involvement. Thus, thermography is not helpful in the diagnosis of these two common entrapment neuropathies.

Position of the wrist associated with the lowest carpal-tunnel pressure: implications for splint design.

Increased carpal-tunnel pressure has been implicated in the pathophysiology of carpal tunnel syndrome, but it is not known whether splints that immobilize the wrist in a functional position of extension minimize carpal tunnel pressure. To determine the position of the wrist that results in the lowest carpal-tunnel pressure, twenty control subjects and four patients who had carpal tunnel syndrome were evaluated with use of a new, dynamic method that continuously measures carpal tunnel pressure throughout the range of motion of the wrist. The pressure was measured by means of a pressure transducer connected to a flexible catheter that had been inserted into the carpal canal. The position of the wrist was measured simultaneously with use of a two-axis electrogoniometer. Aided by a computer monitor that displayed a moving line of real-time carpal-tunnel pressure, each subject was instructed to move the wrist throughout the range of motion and to adjust it to the position that corresponded to the lowest carpal-tunnel pressure. For the control subjects, the lowest carpal-tunnel pressure averaged 8 +/- 4 millimeters of mercury (1.07 +/- 0.53 kilopascals), and the average position of the wrist associated with the lowest pressure was 2 +/- 9 degrees of extension and 2 +/- 6 degrees of ulnar deviation.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of serum prolactin in diagnosing epileptic seizures: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Objective: The purpose of this article is to review the use of serum prolactin assay in epileptic seizure diagnosis. Methods: The authors identified relevant studies in multiple databases and reference lists. Studies that met inclusion criteria were summarized and rated for quality of evidence, and the results were analyzed and pooled where appropriate. Results: Most studies used a serum prolactin of at least twice baseline value as abnormal. For the differentiation of epileptic seizures from psychogenic nonepileptic seizures, one Class I and seven Class II studies showed that elevated serum prolactin was highly predictive of either generalized tonic–clonic or complex partial seizures. Pooled sensitivity was higher for generalized tonic–clonic seizures (60.0%) than for complex partial seizures (46.1%), while the pooled specificity was similar for both (approximately 96%). Data were insufficient to establish validity for simple partial seizures. Two Class II studies were consistent in showing prolactin elevation after tilt-test–induced syncope. Inconclusive data exist regarding the value of serum prolactin following status epilepticus, repetitive seizures, and neonatal seizures. Recommendations: Elevated serum prolactin assay, when measured in the appropriate clinical setting at 10 to 20 minutes after a suspected event, is a useful adjunct for the differentiation of generalized tonic–clonic or complex partial seizure from psychogenic nonepileptic seizure among adults and older children (Level B). Serum prolactin assay does not distinguish epileptic seizures from syncope (Level B). The use of serum PRL assay has not been established in the evaluation of status epilepticus, repetitive seizures, and neonatal seizures (Level U).

HIV neuropathy natural history cohort study: assessment measures and risk factors.

Background: Distal sensory polyneuropathy (DSP) is the most common neurologic complication of human immunodeficiency virus (HIV) infection. Risk factors for DSP have not been adequately defined in the era of highly active antiretroviral therapy. Methods: The authors evaluated 101 subjects with advanced HIV infection over 48 weeks. Assessments included a brief peripheral neuropathy (PN) screen (BPNS), neurologic examination, nerve conduction studies, quantitative sensory testing (QST), and skin biopsies with quantitation of epidermal nerve fiber density. Data were summed into a Total Neuropathy Score (TNS). The presence, severity, and progression of DSP were related to clinical and laboratory results. Results: The mean TNS (range 0 to 36) was 8.9, with 38% of subjects classified as PN-free, 10% classified as having asymptomatic DSP, and 52% classified as having symptomatic DSP. Progression in TNS from baseline to week 48 occurred only in the PN-free group at baseline (mean TNS change = 1.16 ± 2.76, p = 0.03). Factors associated with progression in TNS were lower current TNS, distal epidermal denervation, and white race. As compared with the TNS diagnosis of PN at baseline, the BPNS had a sensitivity of 34.9% and a specificity of 89.5%. Conclusions: In this cohort of advanced human immunodeficiency virus (HIV)–infected subjects, distal sensory polyneuropathy was common and relatively stable over 48 weeks. Previously established risk factors, including CD4 cell count, plasma HIV RNA, and use of dideoxynucleoside antiretrovirals were not predictive of the progression of distal sensory polyneuropathy (DSP). Distal epidermal denervation was associated with worsening of DSP. As compared with the Total Neuropathy Score, the brief peripheral neuropathy screen had relatively low sensitivity and high specificity for the diagnosis of DSP.