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J Jankovic

Publications and source records attributed to J Jankovic.

At least 19 recordsLinked to original sources

Multiple system atrophy: the putative causative role of environmental toxins.

BACKGROUND: Whereas a number of studies have investigated the putative role of environmental toxins in the pathogenesis of idiopathic Parkinson disease, the possibility of such a role in multiple system atrophy has received little attention. DESIGN AND SETTING: Review of records of patients examined in the Parkinson's Disease Center and Movement Disorder Clinic, Baylor College of Medicine, Houston, Tex, from July 1, 1977, to February 4, 1998. PATIENTS: We reviewed 100 consecutive medical records of patients who satisfied the diagnostic criteria for multiple system atrophy formulated by the Consensus Committee of the American Autonomic Society and the American Academy of Neurology. INTERVENTION: The type and amount of toxin exposure were verified by history and examination of records whenever possible. Severity of parkinsonism was assessed by clinical rating scales. MAIN OUTCOME MEASURE: Development of multiple system atrophy after environmental toxin exposure. RESULTS: Eleven patients had a notable history of heavy exposure to environmental toxins. One patient with multiple system atrophy confirmed by postmortem evaluation was exposed to high concentrations of malathion, diazinon, and formaldehyde, while the other patients with multiple system atrophy had well-documented high exposures to agents including n-hexane, benzene, methyl isobutyl ketone, and pesticides. The case studied pathologically demonstrated extensive advanced glial changes, including glial cytoplasmic inclusions in deep cerebellar white matter, brainstem, cortex (superior frontal, insula) and putamen, with notable cell loss and depigmentation of the substantia nigra and locus ceruleus. CONCLUSION: While many studies report a possible role of environmental toxins in Parkinson disease, such a role is even more likely in multiple system atrophy, as this is a sporadic disease.

Environmental Pollutants

Clinical correlates of vascular parkinsonism.

BACKGROUND: Parkinsonism may be due to other causes besides Parkinson disease (PD). Vascular parkinsonism (VP) has not been well defined and the clinical correlates of VP have not been clarified. OBJECTIVES: To seek evidence for or against the role of cerebrovascular disease in parkinsonism, and to identify clinical features that suggest a vascular origin. DESIGN: Retrospective chart review of patients with parkinsonism. A vascular rating scale was used to identify 2 patient groups, 1 with strong evidence of cerebrovascular disease (VP), and 1 with idiopathic PD. Clinical features of parkinsonism were then compared between the 2 patient groups. SETTING: A Movement Disorders Clinic, Baylor College of Medicine, Houston, Tex, a tertiary referral center. PATIENTS: Three hundred forty-six patients, 69 with VP and 277 with PD. RESULTS: The VP and PD groups were clearly differentiated in terms of evidence of cerebrovascular disease (P<.001 to P<.00001). Patients with VP were older, more likely to present with gait difficulty rather than tremor, and less likely to respond to the use of levodopa compared with patients with PD (P<.00001). Patients with VP were also significantly more likely to have predominant lower body involvement, postural instability, a history of falling, dementia, corticospinal findings, incontinence (P<.00001), and pseudobulbar effect (P<.05). CONCLUSIONS: These differences in clinical features suggest a different pathogenesis of parkinsonism in these 2 patient groups. The strong evidence of cerebrovascular disease in the VP group and the differences in clinical features support the concept of VP as a distinct clinical entity. We conclude that compared with PD, patients with parkinsonism associated with vascular disease are more likely to present with gait difficulty and postural instability rather than tremor, have a history of stroke and risk factors for stroke, and fail to respond to levodopa therapy.

Aged

Movement and reaction times and fine coordination tasks following pallidotomy.

The effect of a unilateral, microelectrode-guided lesion in the globus pallidum internum (GPi) was evaluated in 41 patients (21 women) with moderately advanced Parkinson's disease (PD). The mean age was 60.3+/-9.0 years (range, 40-74) and the mean symptom duration was 14.7+/-5.3 years (range, 4-25). In addition to clinical ratings, movement time (MT) and reaction time (RT) tests were performed at baseline and 3 months after surgery during the "practically defined off" state (more than 12 hours after the last dose of levodopa). Improvement occurred bilaterally with more robust and statistically significant improvement on the contralateral side in all RT tests. Simple reaction time (SRT) improved by 14.5% (p<0.001) and the choice reaction time (CRT) by 12.2% (p<0.001) when the arm contralateral to the pallidotomy side was tested. There was a trend toward improvement in the ipsilateral arm. The MT, determined by repetitive movement between two adjacent targets, improved by 24% contralaterally (p<0.0001) and by 12% ipsilaterally (p<0.005). In addition, the Purdue Pegboard (PP) test scores, used to evaluate hand dexterity, improved on the contralateral side by 35.5% (p<0.0002) but there was no statistically significant ipsilateral improvement. To the extent that MT and RT are quantitative measures of bradykinesia, our study provides evidence that this parkinsonian feature improves after pallidotomy.

Adult

The G209A mutation in the alpha-synuclein gene is not detected in familial cases of Parkinson disease in non-Greek and/or Italian populations.

OBJECTIVE: To determine whether the G-to-A substitution at nucleotide 209 (G209A) mutation in the alpha-synuclein gene is responsible for familial Parkinson disease (PD) in the US population. DESIGN: Polymerase chain reaction-based DNA analysis of consecutive patients with PD and family history of PD. SETTING: A university-affiliated movement disorder clinic and a Veterans Affairs clinical research laboratory. PATIENTS: Forty-four patients with PD and family history of PD and 29 patients with sporadic PD, all with no known Greek and/or Italian background. RESULTS: None of the DNA samples showed the G209A mutation. CONCLUSION: The G209A mutation is rare in US patients with familial PD.

Adult

Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study.

BACKGROUND: Whether Parkinson disease (PD) and dementia with Lewy bodies (DLB) represent 2 distinct nosologic entities or are diverse phenotypes of Lewy body disease is subject to debate. OBJECTIVES: To determine the accuracy of the diagnoses of Lewy body disease, PD, and DLB by validating the clinical diagnoses of 6 neurologists with the neuropathologic findings and to identify early predictors of the diagnoses. METHODS: Six raters who were unaware of the neuropathologic diagnoses analyzed 105 clinical vignettes corresponding to 29 cases of Lewy body disease (post hoc analysis of 15 patients with PD and 14 with DLB) and 76 patients without PD or DLB whose cases were confirmed through autopsy findings. MAIN OUTCOME MEASURES: Sensitivity and positive predictive value (PPV) were chosen as validity measures and the K statistic as a reliability measure. RESULTS: Interrater reliability for the diagnoses of Lewy body disease and PD was moderate for the first visit and substantial for the last, whereas agreement for diagnosis of DLB was fair for the first visit and slight for the last. Median sensitivity for diagnosis of Lewy body disease was 56.9% for the first visit and 67.2% for the last; median PPV was 60.0% and 77.4%, respectively. Median sensitivity for the diagnosis of PD was 73.3% for the first visit and 80.0% for the last; median PPV was 45.9% and 64.1%, respectively. Median sensitivity for the diagnosis of DLB was 17.8% for the first visit and 28.6% for the last; median PPV was 75.0% for the first visit and 55.8% for the last. The raters' results were similar to those of the primary neurologists. Several features differentiated PD from DLB, predicted each disorder, and could be used as clinical pointers. CONCLUSIONS: The low PPV with relatively high sensitivity for the diagnosis of PD suggests overdiagnosis. Conversely, the extremely low sensitivity for the diagnosis of DLB suggests underdiagnosis. Although the case mix included in the study may not reflect the frequency of these disorders in practice, limiting the clinical applicability of the validity measures, the raters' results were similar to those of the primary neurologists who were not exposed to such limitations. Overall, our study confirms features suggested to predict these disorders, except for the early presence of postural imbalance, which is not indicative of either disorder.

Adult

Hemifacial spasm: clinical findings and treatment.

Hemifacial spasm (HFS) is a peripherally induced movement disorder characterized by involuntary, unilateral, intermittent, irregular, tonic or clonic contractions of muscles innervated by the ipsilateral facial nerve. We reviewed the clinical features and response to different treatments in 158 patients (61% women) with HFS evaluated at our Movement Disorders Clinic. The mean age at onset was 48.5+/-14.1 years (range: 15-87) and the mean duration of symptoms was 11.4+/-8.5 (range: 0.5-53) years. The left side was affected in 56% instances; 5 patients had bilateral HFS. The lower lid was the most common site of the initial involvement followed by cheek and perioral region. Involuntary eye closure which interfered with vision and social embarrassment were the most common complaints. HFS was associated with trigeminal neuralgia in 5.1% of the cases and 5.7% had prior history of Bell's palsy. Although vascular abnormalities, facial nerve injury, and intracranial tumor were responsible for symptoms in some patients, most patients had no apparent etiology. Botulinum toxin type A (BTX-A) injections, used in 110 patients, provided marked to moderate improvement in 95% of patients. Seven of the 25 (28%) patients who had microvascular decompression reported permanent complications and the HFS recurred in 5 (20%). Although occasionally troublesome, HFS is generally a benign disorder that can be treated effectively with either BTX-A or microvascular decompression.

Adult

Variability of the immunologic and clinical response in dystonic patients immunoresistant to botulinum toxin injections.

Immunoresistance (Ab+) to botulinum toxin type A (BTX-A) has been a serious concern since the introduction of BTX-A in the treatment of dystonia and other disorders associated with abnormal muscle contractions. We studied seven patients who developed Ab+ and later reverted to antibody-negative (Ab-) status. These seven patients, six women (mean age, 56 years; range, 41-80 years), with an average duration of dystonia for all patients of 197 months (range, 84-360 months), received a total mean cumulative dose of 1659 units (U) (range, 810-1975 U), with an average dose of 207 U per visit. All of these patients became unresponsive to BTX-A treatment and became Ab+ as determined by mouse bioassay. Their response to BTX-A after they reverted to Ab- was analyzed. The average latency between the initial BTX-A treatment and development of Ab+ was 27 months (range, 1543 months). The average duration between the detection of Ab+ status and subsequent reversal to Ab- status was 30 months (range, 10-78 months). Six of these Ab- patients were reinjected with BTX-A, and all six benefited from repeat injections comparable with their earlier response. Three patients lost their clinical response to subsequent injections and were found to be again Ab+. Two of the five patients who became immunoresistant to BTX-A received botulinum toxin type F (BTX-F) injections and one patient received a single session of BTX-B with improvement in their symptoms. In conclusion, this unique group of patients who were Ab+ and became Ab- responded favorably to repeat BTX-A injections, but some lost the benefit with subsequent injections. These observations suggest that the anamnestic immunologic response to BTX-A can wane, but can be reactivated by repeat BTX-A treatments. The presence of antibodies did not interfere with the response to BTX-F or BTX-B injections, thus confirming the antigenic specificity of various BTX serotypes.

Aged

Pallidotomy for generalized dystonia.

We systematically evaluated the efficacy of both unilateral and bilateral stereotactic pallidotomy in eight patients with generalized dystonia. Six patients had a marked improvement in dystonic movements and motor function; the other two patients also benefited from the procedure but to a lesser extent. The severity of dystonia was assessed before and after surgery by the Burke-Marsden-Fahn Dystonia Scale (BMFDS), the Unified Dystonia Rating Scale (UDRS), and the Activity of Daily Living Scale (ADL). The BMFDS scores decreased by 59.0%, UDRS by 62.5%, and ADL by 47.8% postoperatively. Adverse events were limited to a transient weakness in one patient. We conclude that pallidotomy is a safe and effective treatment in medically refractory cases of generalized dystonia.

Activities of Daily Living

Evidence that a gene for essential tremor maps to chromosome 2p in four families.

In this Journal, we previously reported genetic linkage between loci on chromosome (chr)2p(ETM) and dominantly inherited essential tremor (ET) in a large American kindred of Czech ancestry. Other investigators reported another ET susceptibility locus on chr 3q (FET1) which accounted for over half of the Icelandic families that were studied. We now report evidence for linkage to the ETM locus in three additional, unrelated American families with ET and exclude the FET1 locus in these families. Fine mapping results, using an "affecteds-only" model in all four American families, demonstrate positive combined pairwise lod scores (Z) at the ETM locus with aZ(max) = 5.94 at a recombination fraction (theta) = 0.00 for locus D2S220. Haplotype reconstruction places the ETM gene in a 9.10 cM interval between the D2S224 and D2S405 loci. Multipoint linkage analysis suggests that the ETM gene is in the 2.18 cM interval between loci D2S2150 and D2S220 with a Z(max) = 8.12. These findings may facilitate the search for a gene that causes ET and may further our understanding of other disorders that are associated with tremor [corrected].

Adult

Retrospective application of a set of clinical diagnostic criteria for the diagnosis of multiple system atrophy.

We estimated the accuracy of a modified commonly used set of clinical diagnostic criteria for the diagnosis of multiple system atrophy (MSA) by retrospectively applying the criteria to the features recorded by six neurologists who had evaluated 105 autopsy-confirmed cases (16 MSA and 89 non-MSA disorders). Cases were abstracted from the records of the patients' first visit to an academic center, and were presented as clinical vignettes to six neurologists, each of whom recorded the main clinical features of the presented clinical vignette on a standardized form. Sensitivity and positive predictive values were chosen as validity outcome measures and were calculated by comparing the applied diagnostic criteria to the neuropathologic information. Of note, most MSA patients in this study (mainly those with Shy-Drager type) had not received levodopa therapy since the primary neurologists often had not perceived a need to administer this treatment. The validity of the retrospectively applied criteria for the diagnosis of possible MSA (sensitivity: median, 53%, range, 50-69%; positive predictive value: 30%, 28-39%) and probable MSA (sensitivity: 44%, 31-60%; positive predictive value: 68%, 54-80%) at the first visit was suboptimal. The best, still not perfect, accuracy for this set of diagnostic criteria was obtained when six out of eight features (sporadic adult onset, dysautonomia, parkinsonism, pyramidal signs, cerebellar signs, no levodopa response, no cognitive dysfunction, or no downward gaze supranuclear palsy) were present (median sensitivity, 59%; range, 50-75%; positive predictive value: 67%, 53-83%). This is the first study to validate criteria for the clinical diagnosis of MSA. Our data suggest that it is difficult to achieve an early and accurate clinical diagnosis of this disorder. The probability of correctly diagnosing MSA increases when at least six features of this modified set of criteria are present or when requiring the set for probable MSA.

Adult

Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination.

OBJECTIVE: To analyse the natural history and survival of corticobasal degeneration by investigating the clinical features of 14 cases confirmed by postmortem examination. METHODS: Patients with definite corticobasal degeneration were selected from the research and clinical files of seven tertiary medical centres in Austria, the United Kingdom, and the United States. Clinical features were analysed in detail. RESULTS: The sample consisted of eight female and six male patients; mean age at symptom onset was 63 (SD 7.7) years, and mean disease duration was 7.9 (SD 2.6) years. The most commonly reported symptom at onset included asymmetric limb clumsiness with or without rigidity (50%) or tremor (21%). At the first neurological visit, on average 3.0 (SD 1.9) years after symptom onset, the most often encountered extrapyramidal features included unilateral limb rigidity (79%) or bradykinesia (71%), postural imbalance (45%), and unilateral limb dystonia (43%). Ideomotor apraxia (64%), and to a lesser extent cortical dementia (36%), were the most common cortical signs present at the first visit. During the course of the disease, virtually all patients developed asymmetric or unilateral akinetic rigid parkinsonism and a gait disorder. No patient had a dramatic response to levodopa therapy. Median survival time after onset of symptoms was 7.9 (SD 0.7) (range, 2.5-12.5) years, and, after the first clinic visit, 4.9 (SD 0.7) (range, 0.8-10) years. Early bilateral bradykinesia, frontal syndrome, or two out of tremor, rigidity, and bradykinesia, predicted a shorter survival. CONCLUSION: The results confirm that unilateral parkinsonism unresponsive to levodopa and limb ideomotor apraxia are the clinical hallmarks of corticobasal degeneration, and only a minority of patients with corticobasal degeneration present with dementia. The study also suggests that a focal cognitive and extrapyramidal motor syndrome is indicative of corticobasal degeneration. Survival in corticobasal degeneration was shortened by the early presence of (more) widespread parkinsonian features or frontal lobe syndrome.

Aged

Peripherally induced oromandibular dystonia.

OBJECTIVES: Oromandibular dystonia (OMD) is a focal dystonia manifested by involuntary muscle contractions producing repetitive, patterned mouth, jaw, and tongue movements. Dystonia is usually idiopathic (primary), but in some cases it follows peripheral injury. Peripherally induced cervical and limb dystonia is well recognised, and the aim of this study was to characterise peripherally induced OMD. METHODS: The following inclusion criteria were used for peripherally induced OMD: (1) the onset of the dystonia was within a few days or months (up to 1 year) after the injury; (2) the trauma was well documented by the patient's history or a review of their medical and dental records; and (3) the onset of dystonia was anatomically related to the site of injury (facial and oral). RESULTS: Twenty seven patients were identified in the database with OMD, temporally and anatomically related to prior injury or surgery. No additional precipitant other than trauma could be detected. None of the patients had any litigation pending. The mean age at onset was 50.11 (SD 14.15) (range 23-74) years and there was a 2:1 female preponderance. Mean latency between the initial trauma and the onset of OMD was 65 days (range 1 day-1 year). Ten (37%) patients had some evidence of predisposing factors such as family history of movement disorders, prior exposure to neuroleptic drugs, and associated dystonia affecting other regions or essential tremor. When compared with 21 patients with primary OMD, there was no difference for age at onset, female preponderance, and phenomenology. The frequency of dystonic writer's cramp, spasmodic dysphonia, bruxism, essential tremor, and family history of movement disorder, however, was lower in the post-traumatic group (p<0.05). In both groups the response to botulinum toxin treatment was superior to medical therapy (p<0.005). Surgical intervention for temporomandibular disorders was more frequent in the post-traumatic group and was associated with worsening of dystonia. CONCLUSION: The study indicates that oromandibular-facial trauma, including dental procedures, may precipitate the onset of OMD, especially in predisposed people. Prompt recognition and treatment may prevent further complications.

Adolescent

Assessment of motor function after stereotactic pallidotomy.

Despite a paucity of controlled data, stereotactic pallidotomy is increasingly used for the treatment of advanced Parkinson's disease (PD). To study the efficacy of the procedure on the cardinal PD features of rigidity, tremor, bradykinesia, and postural instability, we blindly rated randomized videos of 34 patients recorded in the "off' state immediately before and 3 months after unilateral stereotactic lesioning of the globus pallidus internus. Total "off' time Unified Parkinson's Disease Rating Scale motor scores improved 13.6% from 28.9 +/- 7.5 to 25.0 +/- 7.0 (p < 0.001). Particularly robust improvement was seen in contralateral tremor, gait, and arising from a chair (p < 0.001). Significant improvement was also seen in ipsilateral tremor, contralateral and some ipsilateral dexterity measures, and body bradykinesia. Most other features tended toward improvement but did not reach statistical significance. We conclude that pallidotomy is a safe and effective treatment of parkinsonian symptoms, many of which improve bilaterally.

Adult

Mouse bioassay versus Western blot assay for botulinum toxin antibodies: correlation with clinical response.

OBJECTIVE: To compare the mouse protection bioassay (MPB) to the Western blot assay (WBA) in detecting antibodies against botulinum toxin A (BTX-A) and to correlate the assay results with clinical responses to BTX-A injections. METHODS: MPB and WBA assay results were compared in 51 patients (34 nonresponders and 17 responders) who received BTX-A injections, most commonly for cervical dystonia. A subset of patients received a "test" injection into either the right eyebrow (14) or right frontalis (12). RESULTS: Twelve patients with antibodies against BTX-A (Ab+) detected by WBA did not demonstrate antibodies (Ab-) by MPB. Conversely, five patients were Ab+ by MPB but Ab- by WBA. Specificity of the MPB was 100% on all three parameters (clinical, eyebrow, and frontalis injections), whereas WBA specificity was only 71% for clinical response but 100% for both eyebrow and frontalis responses. Sensitivities for both assays were low (33 to 53%). Of the 16 patients previously Ab+ by MPB, seven became negative on retesting after a mean interval of 33 months (range, 6 to 93 months). CONCLUSIONS: The lower specificity of the WBA compared to the MPB suggests that the WBA detects nonblocking antibodies. Eyebrow and frontalis "test" injections correlated well with MPB and WBA results and with clinical responses and may be useful in the evaluation of BTX nonresponders.

Adult

Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson's disease tremor.

OBJECTIVE: To determine the efficacy and tolerability of unilateral thalamic deep brain stimulation (DBS) for patients with medically refractory essential tremor (ET) and the tremor associated with Parkinson's disease (PD). BACKGROUND: The tremor of ET and PD may produce functional disability despite optimal medical therapy. Several reports have demonstrated efficacy of thalamic DBS in this scenario. METHODS: Preoperative and 3-month postoperative tremor ratings were compared in 33 patients (14 ET and 19 PD) with severe tremor. Evaluations included Unified Parkinson's Disease Rating Scale (UPDRS) scores for PD patients and a modified Unified Tremor Rating Scale in ET patients. Open-label and blinded data (unknown activation status) were obtained. RESULTS: ET patients demonstrated an 83% reduction (p < 0.0001) in observed contralateral arm tremor. All measures of tremor including writing samples, pouring tests, subjective functional surveys, and disability scores improved significantly. PD patients demonstrated an 82% reduction (p < 0.0001) in contralateral tremor and significant improvement in disability and global impressions. There was, however, no meaningful improvement in other motor aspects of the disease, and the total UPDRS part II (activities of daily living) score did not change. Adverse events, more common in ET patients, were generally mild and were usually eliminated by adjustment of the device parameters. CONCLUSIONS: Thalamic DBS is a safe and effective treatment of ET and the tremor of PD. In PD, its use should be limited to patients in whom high-amplitude tremor results directly in significant functional disability.

Aged

Posteroventral medial pallidotomy for treatment of Parkinson's disease: preoperative magnetic resonance imaging features and clinical outcome.

OBJECT: The goal of this study was to investigate the impact of mild or moderate degrees of degenerative or ischemic encephalopathy on predicting clinical outcome following unilateral posteroventral medial pallidotomy for treatment of advanced Parkinson's disease (PD). METHODS: Thirty-five patients with PD were studied prospectively. The presence and degree of cortical atrophy, ventriculomegaly, deep white matter lesions (DWML), periventricular lucencies (PVL), and the presence of lacunes and status cribriformis (multiple and bilateral enlarged Virchow-Robin spaces) were determined by magnetic resonance (MR) imaging before the patients underwent stereotactic pallidotomy performed according to a standard protocol. Clinical outcome was measured using a standard battery of tests including application of the Unified Parkinson's Disease Rating Scale (UPDRS). The preoperative MR imaging features were correlated with UPDRS subscores such as motor "off' score, the activities of daily living (ADL) off score, the off subscore for bradykinesia, the percentage of "on" time dyskinesias, and a global outcome rating. The MR findings were also correlated with the occurrence of side effects. Global outcome was rated as markedly improved in 22 patients (63%) and as moderately improved in 12 patients (34%) 6 months postoperatively. At the 1-year follow-up examination, global outcome in 31 patients was rated as markedly improved in 14 patients (45%), as moderately improved in another 14 (45%), as slightly improved in two (6%), and as worse in one patient (3%). The mean UPDRS motor off score changed from 58.7 preoperatively to 33.2 at 6 months and 33.4 at 1 year (p < 0.0001), the ADL off score from 31.8 to 18.2 at 6 months and 18.6 at 1 year (p < 0.0001), the off score from contralateral bradykinesia from 11.6 to 5.6 at 6 months and 4.1 at 1 year (p < 0.0001), and the percentage of awake time with dyskinesias from 37.4 to 17.4% at 6 months and 21.1% at 1 year (p < 0.0001). The presence of mild or moderate degrees of cortical atrophy, PVL, and DWML had no effect on clinical outcome. Patients with status cribriformis and those with lacunes tended to show comparatively less improvement in the UPDRS ADL off score (p = 0.014 and p = 0.016, respectively) at 6 months. This tendency was also present in patients with status cribriformis 1 year postoperatively (p = 0.046). Patients with both status cribriformis and lacunes had a higher incidence of transient altered mental status immediately postoperatively (p = 0.05). CONCLUSIONS: Mild-to-moderate degrees of cortical atrophy, ventriculomegaly, and ischemic encephalopathy do not predispose patients to less favorable outcomes following unilateral pallidotomy. Patients with both status cribriformis and lacunes have a higher risk of transient side effects; however, with regard to clinical outcome, these patients should not be denied surgical treatment.

Activities of Daily Living