Long-Time Course of Idiopathic Small Fiber Neuropathy.

BACKGROUND: Small fiber neuropathy (SFN) is a challenging subtype of peripheral neuropathies. Once the diagnosis has been established, there is an uncertainty how SFN may progress, whether larger fibers will become involved over time, whether quality of life may be compromised, or whether repeated diagnostic workup in patients with unknown underlying cause may increase the yield of treatable causes of SFN. METHODS: We evaluated 16 patients with documented long-time course of idiopathic SFN. RESULTS: Clinical and electrophysiological course remained stable in 75% of the patients, while 25% SFN-patients developed large fiber neuropathies. CONCLUSIONS: Our data suggest that SFN represents a benign disease course in the majority of patients without severely limiting the quality of life.

Prognostic value of somatosensory evoked potentials, neuron-specific enolase, and S100 for short-term outcome in ischemic stroke.

To predict short-term outcome in acute ischemic stroke, we analyzed somatosensory evoked potentials (SEP) and biochemical parameters [neuron-specific enolase (NSE) and S100 protein] in a prospective study with serial measurement. In 31 patients with 1st middle cerebral artery infarction, serum NSE and S100 protein were measured daily between days 1 and 6 poststroke. The N20 and N70 components of the SEP (SEP20 and SEP70) were determined on days 1 and 6. SEP and biochemical markers in stroke patients were compared with a control group. Short-term outcome was assessed by the modified Rankin Scale (mRS) at days 7-10 and was dichotomized between good (mRS 0-2) and poor (mRS ≥3) outcome. Specificity and positive predictive value (PPV) were high at day 1 for SEP (SEP20: 100% for both; SEP70: 93 and 88%, respectively) compared with lower values for NSE (67 and 50%) and S100 (23 and 57%). In contrast, S100 showed the highest sensitivity at day 1 with 77% compared with a relatively low sensitivity of NSE (31%) and SEP (SEP20: 35%, SEP70: 47%). The biochemical markers showed an improving sensitivity over time with best values (>90%) between days 3 and 4 at the expense of a lower specificity. Specificity and PPV of SEP on day 6 was still 100% with sensitivity increasing up to 53% (SEP20) and 60% (SEP70). SEP could early differentiate between good and poor outcome and reliably predict poor outcome. Since biochemical markers and SEP complement each other in the prognosis of stroke, a combined application of these markers seems promising.

Changes in neuron-specific enolase are more suitable than its absolute serum levels for the prediction of neurologic outcome in hypothermia-treated patients with out-of-hospital cardiac arrest.

BACKGROUND: To determine neurologic outcome in patients with out-of-hospital cardiac arrest (OHCA) and treatment with mild therapeutic hypothermia (MTH). METHODS: Seventy-three consecutive OHCA patients treated with MTH were retrospectively analyzed. Serum neuron-specific enolase (NSE) was measured 24, 48, and 72 h after admission. In patients with no motor response 48 h after termination of analgosedation (n = 40), clinical neurological examination and evoked potentials (EPs) were determined. Neurological outcome was assessed after 2 months based on the cerebral performance categories (CPC), and categorized as good (CPC 1-3) or poor (CPC 4 and 5). RESULTS: Forty-three patients had a CPC score of 1-3 and 30 patients had a CPC 4-5. The best predictive value for poor neurologic outcome was an increase of NSE by ≥4.3 ng/mL between day 1 and day 2 (sensitivity 80 %, specificity 100 %, positive predictive value (PPV) 100 %, negative predictive value 86 %). Absolute NSE values were less reliable in the prediction of poor outcome with the highest sensitivity (88 %) and specificity (95 %) if values reached ≥36.3 ng/mL on day 3. Somatosensory EPs (SSEPs) showed a specificity of 100 % and PPV of 100 %; however, sensitivity for evoked potentials was low (29 %). Intriguingly, two initially comatose patients with excessive NSE values (24 h NSE: 101 and 256 ng/mL, and 48 h NSE: 93 and 110 ng/mL, respectively) had physiological SSEPs and regained a CPC score of 1. CONCLUSION: In patients treated with MTH after OHCA changes in NSE are more suitable than its absolute serum levels for the prediction of poor neurologic outcome. Since unequivocal prediction of poor neurologic outcome is of utmost importance in these patients the decision to limit therapy must be based on several prediction tools with the highest PPV and specificity including SSEPs.

Prognostic value of electroencephalography and evoked potentials in the early course of malignant middle cerebral artery infarction.

Space-occupying brain edema may lead to a malignant course in patients with large middle cerebral artery infarction. Decompressive hemicraniectomy has to be initiated early to prevent further tissue damage. In this retrospective study, we analyzed electroencephalography (EEG) and evoked potentials (EPs), obtained within 24 h after onset of stroke, in 22 patients suffering from a large middle cerebral artery infarction. Our findings indicate a prognostic value of EEG and brainstem auditory EP (BAEP): the absence of delta activity and the presence of theta and fast beta frequencies within EEG-focus predicted a non-malignant course. In contrast, diffuse generalized slowing and slow delta activity in the ischemic hemisphere pointed to a malignant course. Likewise, pathological BAEP were correlated with a malignant course. The coexistence of background slowing and pathological BAEP showed the highest level of significance. In conclusion, our findings implicate an additional early application of electrophysiological methods in stroke patients. EEG and EP deliver useful information to select those patients who develop malignant edema.

Immunoadsorption in patients with chronic inflammatory demyelinating polyradiculoneuropathy with unsatisfactory response to first-line treatment.

BACKGROUND/AIMS: First-line treatment options for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are corticosteroids, intravenous immunoglobulin, and plasma exchange. In a significant number of patients, first-line therapy fails, and long-term maintenance treatment still remains a therapeutic challenge. Immunoadsorption (IA) may be an alternative to classical plasma exchange in the therapy of immune-mediated neurologic diseases. The aim of this investigation was to evaluate efficacy and safety of IA in patients with CIDP with unsatisfactory response to first-line treatment options. METHODS: CIDP patients received adjunct IA treatment using tryptophan-immune adsorbers. The inflammatory neuropathy cause and treatment disability (INCAT) score was used to grade disability and monitor treatment effects. RESULTS: In total, 14 CIDP patients were analyzed. Ten patients were treated in hospital. After one IA treatment series, the INCAT score decreased significantly in all 10 patients. Four of these 14 patients were treated in outpatient clinics using long-term maintenance IA with 1-2 treatments per week. In these 4 patients, effects of long-term maintenance IA resulted in an improvement of overall disability. In all patients, IA was safe, well tolerated, and no severe adverse effects occurred. CONCLUSION: IA could be an effective and safe option for CIDP patients with unsatisfactory response to first-line treatment options and for long-term maintenance treatment.

Altered cerebral glucose metabolism in a family with clinical features resembling mitochondrial neurogastrointestinal encephalomyopathy syndrome in association with multiple mitochondrial DNA deletions.

OBJECTIVE: To determine the involvement of cerebral metabolism in 2 siblings with mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE)-like disease with multiple mitochondrial DNA (mtDNA) deletions. DESIGN: Case report. SETTING: Department of Neurology at a university medical center. PATIENTS: Two siblings with MNGIE-like disease with multiple mtDNA deletions. MAIN OUTCOME MEASURES: Clinical, biochemical, genetic, and imaging findings, including cerebral magnetic resonance imaging, proton magnetic resonance spectroscopy, and positron emission tomography with fluorine 18-labeled deoxyglucose (FDG-PET). RESULTS: Genetic analysis of muscle DNA revealed multiple mtDNA deletions, while no mutations were detected in ECGF1, POLG1, ANT1, or Twinkle. Cerebral magnetic resonance imaging and proton magnetic resonance spectroscopy findings were unremarkable. Reduced regional glucose metabolism was found in a patchy and asymmetrical pattern predominantly in the frontotemporal region in both siblings by means of FDG-PET. CONCLUSIONS: The discrepancy between absence of clinical signs of cerebral involvement and the substantial impairment of glucose metabolism reflects a chronic subclinical encephalopathy. To our knowledge, the predominantly frontotemporal distribution has not been described previously in mitochondrial disorders.

The right inferior frontal gyrus and poststroke aphasia: a follow-up investigation.

BACKGROUND AND PURPOSE: Recently, a combined repetitive transcranial magnetic stimulation (rTMS) and activation positron emission tomography (PET) study showed essential language function of the right inferior frontal gyrus (IFG) in some right-handed acute poststroke aphasics. We reexamined these patients in the chronic phase to test whether the right IFG remained essential for language performance. METHODS: We reexamined 9 male right-handed patients, age 41 to 75 years, with aphasia 8 weeks after left hemispheric stroke. rTMS was performed over the maximum activation within the left and right IFG as defined by (15)[O]water PET to interfere with language function. A positive rTMS effect was defined as increased reaction time latency or error rate in the semantic task relative to no stimulation. RESULTS: PET activations of the IFG were observed on the left (2 patients) and bilaterally (7). During rTMS interference over the left IFG, all patients had positive TMS effects, indicating that the left IFG remained essential. Stimulation over the right IFG yielded positive rTMS effects in 2 patients with persisting right IFG activation. Two patients with positive rTMS effects over the right side in the initial study did not show these effects at follow-up. Language performance improved in all patients. CONCLUSIONS: Successful regeneration from poststroke aphasia seems to depend more on the integration of available language-related brain regions than on recruiting new brain regions during the rehabilitation process. Restoration of the left hemisphere network seems to be more effective, although in some cases, right hemisphere areas are integrated successfully.

Acute loss of vision with hypoplasia of the contralateral carotid artery.

We report a case of a young woman with acute loss of vision of the left eye. The first diagnosis of hypoplasia of the common carotid artery, internal carotid artery, and vertebral artery on the right side was made by means of magnetic resonance angiography. The ischemic optic nerve lesion was caused by a steal phenomenon from the left internal carotid artery to the right cerebral hemisphere with consecutive hypoperfusion of the left ophthalmic artery. Anomalies of the cerebrovascular system should be included in the differential diagnosis of acute loss of vision, even in young patients without cerebrovascular risk factors.

Direct demonstration of transcallosal disinhibition in language networks.

Neuroimaging studies in right-handed patients with left hemisphere brain lesions have demonstrated a shift of language activity from left to right inferior frontal gyrus (IFG). This shift may be caused by greater right hemisphere dominance before the injury or by reduced inhibitory activity of the injured left hemisphere. We simulated a brain lesion applying transcranial -magnetic stimulation over left IFG in normal subjects, while simultaneously measuring language activity with positron -emission tomography. Interference with transcranial -magnetic stimulation decreased activity in left and increased it in right IFG in all subjects. We thus demonstrate for the first time that a rightward shift of language activity is caused by the brain lesion and not by greater right-hemisphere dominance, thus supporting the hypothesis of reduced transcallosal inhibition.

Initial and serial evoked potentials in cerebrovascular critical care patients.

Results of somatosensory evoked potential (SEP) and brainstem auditory evoked potential (BAEP) examinations performed early in the clinical course of patients with acute cerebrovascular disease correlate statistically significantly with outcome regardless of type and localization of the primary lesion. The prognostic value of serial examinations of SEP and BAEP has not been studied yet. The authors examined a group of 215 patients suffering from acute stroke requiring neurocritical care composed of 75 supratentorial and 36 infratentorial ischemic strokes, 58 supratentorial and 18 infratentorial hemorrhages, and 28 aneurysmatic subarachnoid hemorrhages prospectively using spinal and cortical SEP and BAEP according to routine procedures on admission as well as after 1 and 2 weeks. The findings were correlated to outcome at 4 weeks. Statistical assessment was performed using standard methods of contingency analysis. In all groups, SEP findings were significantly correlated with outcome at initial and all subsequent examinations, similar correlations were also found for BAEP. However, after partialling out the prognostic information gained from the initial examination of SEP and BAEP, the follow-up examinations rendered only a marginal increase in prognostic information. Therefore, the initial examination of evoked potentials supplies valuable prognostic information, however, serial examinations of evoked potentials during the first weeks of disease improve the prognostic information only marginally.

From the left to the right: How the brain compensates progressive loss of language function.

In normal right-handed subjects language production usually is a function oft the left brain hemisphere. Patients with aphasia following brain damage to the left hemisphere have a considerable potential to compensate for the loss of this function. Sometimes, but not always, areas of the right hemisphere which are homologous to language areas of the left hemisphere in normal subjects are successfully employed for compensation but this integration process may need time to develop. We investigated right-handed patients with left hemisphere brain tumors as a model of continuously progressive brain damage to left hemisphere language areas using functional neuroimaging and transcranial magnetic stimulation (TMS) to identify factors which determine successful compensation of lost language function. Only patients with slowly progressing brain lesions recovered right-sided language function as detected by TMS. In patients with rapidly progressive lesions no right-sided language function was found and language performance was linearly correlated with the lateralization of language related brain activation to the left hemisphere. It can thus be concluded that time is the factor which determines successful integration of the right hemisphere into the language network for compensation of lost left hemisphere language function.

Role of the contralateral inferior frontal gyrus in recovery of language function in poststroke aphasia: a combined repetitive transcranial magnetic stimulation and positron emission tomography study.

BACKGROUND AND PURPOSE: Functional neuroimaging studies have demonstrated right inferior frontal gyrus (IFG) activation in poststroke aphasia. It remains unclear whether this activation is essential for language performance. We tested this hypothesis in a positron emission tomography (PET) activation study during a semantic task with repetitive transcranial magnetic stimulation (rTMS) on right-handed patients experiencing poststroke aphasia and examined whether rTMS stimulation over the right and left IFG would interfere with language performance. METHODS: Eleven patients with left-sided middle cerebral arterial infarction, 50 to 75 years of age, were tested with the Aachen Aphasia Test Battery and underwent (15)O-H2O PET activation during a semantic task within 2 weeks after stroke. PET activation images were coregistered to T1-weighted MRIs. Stimulation sites were determined on renderings of head and brain over the maximum activation within left and right IFG. rTMS was performed with 20% maximum output (2.1 T), 10-s train duration, at 4 Hz frequency. A positive rTMS effect was defined as an increased reaction time latency or error rate in the semantic task. RESULTS: PET activations of the IFG were observed on the left (3 patients) and bilaterally (8 patients). Right IFG stimulation was positive in 5 patients with right IFG activation, indicating essential language function. In a verbal fluency task, these patients had a lower performance than patients without right-sided TMS effect. CONCLUSIONS: In some poststroke aphasics, right IFG activation is essential for residual language function. However, its compensatory potential seems to be less effective than in patients who recover left IFG function. These results suggest a hierarchy in recovery from poststroke aphasia and a (limited) compensatory potential of the nondominant hemisphere.

Diagnostic value of electromyography in children and adolescents.

The diagnostic accuracy in pediatric neurology has been considerably improved by new methods such as magnetic resonance imaging and molecular genetic analysis. However, standard diagnostic techniques continue to play an important role. The authors analyzed the diagnostic value of electromyography (EMG) and nerve conduction studies (NCS) in a retrospective study of 498 pediatric patients. The overall consistency between EMG results and the final clinical diagnosis in all children examined was 98%. In myogenic diseases, the concordance between EMG and clinical findings was lower (80%), because some patients with congenital myopathies showed normal EMG findings in this group. Peripheral neurogenic diseases were in all but one of the cases diagnosed correctly (99.5%). No decrease in diagnostic reliability was found in the younger age group. EMG and NCS examinations have to be adapted to the needs of children by an experienced examiner, but continue to be valuable diagnostic methods in pediatric neurology.

Coma and cerebral imaging.

The clinical sign of coma is a common feature in critical care medicine. However, little information has been put forth on the correlations between coma and cerebral imaging methods. The purpose of the article is to compile the available information derived from various imaging methods and placing it in a context of clinical knowledge of coma and related states. The definition of coma and the cerebral structures responsible for consciousness are described; the mechanisms of cerebral lesions leading to impaired consciousness and coma are explained. Cerebral imaging methods provide a large array of information on the structural changes of brain tissue in the various diseases leading to coma. Circumscript lesions produce space-occupying masses that displace the brain, ultimately leading to various types of herniation. Generalized disease of the brain usually leads to diffuse brain swelling which also can cause herniation. Epileptic states, however, rarely are detectable by imaging methods and mandate EEG examinations. Another important aspect of imaging in coma is the increasing use of functional imaging methods, which can detect the function of loss of function in various areas of the brain and render information on the extent and severity of brain damage as well as on the prognosis of disease. The MRI methods of (1)H-spectroscopy and diffusion tensor imaging may provide more functional information in the future.

Nerve conduction velocity measurements reveal the functional deficit in ceramide galactosyl transferase-deficient (cgt-/-) mice.

Biochemical and ultrastructural studies of ceramide galactosyltransferase (CGT) in a CGT-deficient mouse line (cgt-/-) were complemented by nerve conduction velocity (NCV) measurements in motor nerves (sciatic nerve in the hind limbs) of wild type (wt) and cgt-/- mice. Stimulation and recording electrodes were adapted to the small size of developing mice during their myelination period. Motor NCVs in wt mice ranged between 16 and 26 m/s but in cgt-/- mice between 6 and 13 m/s, which corresponds to the conductance of unmyelinated peripheral nerves. These electrophysiologic data provide additional functional parameters to the neuropathology of a new form of a dysmyelinosis.

Toll-like receptors promote inflammation in idiopathic inflammatory myopathies.

The roles of Toll-like receptors (TLRs) and their myeloid differentiation response gene 88 (MyD88)-dependent and MyD88-independent signaling cascade particularly with regard to the pathogenesis and regulation of immune responses in idiopathic inflammatory myopathies are unclear. We investigated these pathways in muscle biopsies from 5 cases each of polymyositis, inclusion body myositis, dermatomyositis, vasculitis-associated interstitial myositis, and noninflammatory neurogenic atrophy. Toll-like receptor 2, TLR4, TLR9, and MyD88 mRNA transcripts and protein expression were increased in all subtypes of idiopathic inflammatory myopathies. Upregulation of MyD88 was associated with increased mRNA levels of interferon-γ, interleukin 12p40, and interleukin 17, suggesting NF-κB activation via the MyD88-dependent pathway in early stages. The costimulatory molecules CD80 and CD86 were expressed on inflammatory infiltrates in idiopathic inflammatory myopathies and may additionally contribute to activation of the MyD88-independent pathway, leading to nuclear factor-κB activation in late stages. Our data suggest that nuclear factor-κB activation via both the MyD88-dependent and the MyD88-independent pathways contributes to the proinflammatory milieu in idiopathic inflammatory myopathies.

Application of electrophysiologic techniques in poor outcome prediction among patients with severe focal and diffuse ischemic brain injury.

OBJECTIVE: To explore various electrophysiologic examinations as predictors for poor outcome in patients with severe ischemic brain injury, by comparing the prognostic ability of EEG, short-latency somatosensory evoked potentials (SLSEP), and brain stem auditory evoked potentials (BAEP). METHODS: EEG, SLSEP, and BAEP were recorded in 161 patients with severe ischemic brain injuries (Glasgow Coma Scale ≤ 8), 77 with anoxic-ischemic encephalopathy after cardiopulmonary resuscitation, while 84 experienced massive hemispheric infarction at between 1 and 7 days after the onset. Outcomes were reviewed after 6 months using the Glasgow Outcome Scale. RESULTS: Six months after the onset, poor outcomes (Glasgow Outcome Scale, 1-2) were identified in 66 and 54 patients among the anoxic-ischemic encephalopathy and the massive hemispheric infarction group, respectively. By using the prognostic authenticity analysis of predictors, unfavorable EEG patterns, lack of EEG reactivity, pathologic N20 of SLSEP, and pathologic wave V of BAEP showed the high sensitivity (92.4%-97.0%, 95% confidence interval [CI]: 82.5%-99.5%), while bilateral absence of SLSEP N20 showed the highest specificity (100%, 95% CI: 67.9%-100%) and positive predictive value (100%, 95% CI: 90.4%-100%) in the anoxic-ischemic encephalopathy group. In the massive hemispheric infarction group, unfavorable EEG patterns showed the highest sensitivity (96.3%, 95% CI: 86.2%-99.4%) while bilateral absence of SLSEP N20 and BAEP wave V showed the highest specificity (100%, 95% CI: 85.9%-100%) and positive predictive value (100%, 95% CI: 80.8%-100%). CONCLUSIONS: The predictive power of electrophysiologic examinations is different according to the etiology of ischemic brain injury. Short-latency somatosensory evoked potentials (N20) can be considered the most powerful method to predict poor outcome in anoxic-ischemic encephalopathy. Combination of EEG (unfavorable EEG patterns) and SLSEP (N20)/BAEP (wave V) is best suited in massive hemispheric infarction to predict poor outcome.

Parameters and grading of evoked potentials: prediction of unfavorable outcome in patients with severe stroke.

To explore the prognostic accuracy for unfavorable outcome with short-latency somatosensory evoked potential (SLSEP) and brainstem auditory evoked potential (BAEP) in patients with severe stroke, 100 acute severe supratentorial stroke patients [Glasgow Coma Scale, (GCS) 0.4). Prognostic accuracy of SLSEP, BAEP, and GCS for unfavorable outcome was very high (94.3%-98.7%), among which BAEP is the highest (97.5%-98.7%). The overall prognostic accuracy of SLSEP (90.5%-93.7%) was higher than BAEP (83.0%-89.4%) and GCS (82%). The prognostic accuracy of SLSEP and BAEP for unfavorable outcome in patients with severe supratentorial stroke was high, whereas for favorable outcome, it was low. The overall prognostic accuracy was higher than GCS.

Localizing Broca's area for transcranial magnetic stimulation: Comparison of surface distance measurements and stereotaxic positioning.

BACKGROUND: Precise placement of transcranial magnetic stimulation (TMS) coils over target regions is crucial for correct interpretation of TMS effects. Modern frameless stereotaxic systems yield high accuracy, but require extensive equipment and cannot be used in every setting, for example, during functional imaging sessions. OBJECTIVE: The aim of this study was the development of a method for TMS-coil placement based on individual imaging data without the need for external tracking devices. METHODS: We compared coil positioning over Broca's area using an advanced stereotaxic navigation system with placement according to the surface distance measurements (SDM) method. By using the SDM-method, 3-dimensional renderings adapted from individual T1-weighted magnetic resonance imaging (MRI) data were created to identify Broca's area and Broca's homologue, respectively, and to define anatomic landmarks on the skin's surface. Distances between these landmarks were used to localize the real target on the individual's head. RESULTS: The mean Euclidean distance between surface positions as determined with the two methods was 8.31 mm and the mean difference of estimated virtual electric field intensity at the target point was 7.37 V/m corresponding to 4.01% of maximum field strength. CONCLUSIONS: Our findings suggest that, compared with a state-of-the-art frameless stereotaxy system, the SDM-method yields a reasonable accuracy for positioning of a TMS-coil over Broca's area in terms of spatial coordinates.

Diagnostic value of the electromyography of the extraocular muscles.

OBJECTIVE: The electromyography (EMG) of the extraocular muscles (EOM) represents a special form of electrophysiological investigation techniques which can be offered only in a few centers with special ophthalmologic and neurophysiologic expertise due to its special characteristics. The diagnostic value of the EOM-EMG is especially apparent in neuromuscular diseases which occur with predominantly ocular manifestation. METHODS: Needle EMG examinations of EOM were performed in a cohort of 206 patients with a variety of relevant disorders mainly with a neurological focus. The results of these EMG examinations were assessed retrospectively. After local anaesthesia of the sclera and using a lid retractor to keep the eye open the EOM were identified visually by an experienced ophthalmologist and the needle was inserted. The EMG activity was registered in resting position, in mild volitional, and at maximum activation. The assessment was performed visually on a monitor by an experienced neurophysiologist. RESULTS: In the group of neuromuscular (myopathic) diseases, the results of the EOM-EMG were compatible with the clinical diagnosis in 54 of 65 patients (83%) and in 69 of 85 patients (81%) in the group with peripheral lesions. In a "Varia" group (n=56) no diagnosis could be established despite all further investigations in 31 patients. In the remaining patients, the EOM-EMG result was compatible with the diagnosis in 22 of 25 patients (88%). Subgroup analysis revealed that particularly in myositis (30 of 33 findings in 32 patients, one patient was examined twice; 91%), muscle dystrophy (7 of 8 patients; 88%) and in isolated nerve lesions (64 of 79 patients; 81%) the diagnosis could be positively proven by the EOM-EMG. Clinically relevant complications were not observed. CONCLUSIONS: The EOM-EMG is safe and has a high diagnostic value especially in diseases such as myositis, muscular dystrophy and isolated peripheral nerve lesions. SIGNIFICANCE: With better knowledge of the diagnostic value of the EOM-EMG in various diseases, less relevant diagnostic investigations can be avoided in the future. Moreover, a higher degree of trust in the method should facilitate the decision to perform this special diagnostic method.