Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 52, Num. 4, 2004, pp. 430-435

Neurology India, Vol. 52, No. 4, October-December, 2004, pp. 430-435

Review Article

Continuous EEG monitoring in the evaluation of non-convulsive seizures and status epilepticus

Murthy JMK, Jayashree Naryanan T

Department of Neurology, The Institute of Neurological Sciences, Care Hospital, Hyderabad
Correspondence Address:Department of Neurology, The Institute of Neurological Sciences, CARE Hospital, Exhibition Road, Nampally, Hyderabad - 500 001, jmkmurthy@satyam.net.in

Code Number: ni04148

ABSTRACT

Key Words: Non-convulsive seizures, Non-convulsive status epilepticus, Status epilepticus, Electrographic seizures, Electroencephalogram, Continuous EEG monitoring.

Non-convulsive status epilepticus (NCSE) is an under-diagnosed neurological emergency and is defined as mental status changes from baseline of at least 30 to 60 minutes duration associated with continuous or near continuous ictal discharges on electroencephalogram (EEG).[1] Early recognition and timely intervention is likely to be associated with good outcomes.[2] However, non-convulsive seizure (NCSzs) semilogy is pleomorphic and too subtle clinically to be noticed by clinicians. Most often, mental status impairment is the presenting feature. EEG provides insight into the thalamocortical function in patients with impaired consciousness. Continuous EEG (cEEG) monitoring allows the detection of changes in the function of this system at a reversible stage, often when there are no clinical indications of such phenomena. In addition, EEG provides reasonable spatial resolution and excellent temporal resolution. This makes cEEG an excellent method for supplementing single or serial recordings in the detection and management of NCSzs/NCSE.[3] Previous difficulties associated with the bedside use of the EEG have been largely eliminated with recent advances in digital EEG acquisition, storage, quantitative analysis, and transmission. This has made cEEG monitoring in the neurological intensive care units (NICU) technically feasible.[4]

NCSzs and NCSE - Why cEEG?

Emerging data support a higher than previously thought incidence of non-convulsive epileptic activity in critically ill patients in NICU.[2] Because of the pleomorphic clinical features that can be seen with NCSzs and NCSE, cEEG is the diagnostic cornerstone, and electro-clinical correlation allows rapid diagnosis and management.

NCSzs are not uncommon in critically ill patients in NICU and were recorded in 34% of patients undergoing cEEG in NICU[5] and in 37% of comatose patients without signs of seizure activity.[6] In the Columbia study seizures were detected in 19% of patients who had cEEG monitoring; the seizures were exclusively NCSzs in 92% of patients.[7]

The reported incidence of NCSE in critically ill neurological patients was quite variable and probably related to the patient population studied. In Richmond, Virginia NCSE represented approximately 5% of status epilepticus (SE) cases.[8] In hospital series NCSE constituted approximately 20 to 23% of SE cases,[9],[10] NCSE persisted in 14% of patients after controlling convulsive SE.[11] In VA Cooperative Study,[12] 20% of those with convulsive SE treated successfully clinically, still had electrographic seizures. NCSE was diagnosed in about 8% of all comatose patients without signs of seizure activity.[13] In a group of selected NICU patients, 23 (47%) of 49 patients with NCSzs were in NCSE.[14] In the Columbia study NCSE accounted for 59% of NCSzs.[7] There is hardly any reported data on NCSE from India. In our NICU in the last two years we could identify 22 patients with NCSE and in 50% of them NCSE was identified by cEEG monitoring (unpublished data).

cEEG - Technical Note

Recent advances in digital EEG have made cEEG monitoring in the NICU technically feasible. With digital EEG monitoring, post hoc filtering, re-montaging, adjusting of the sensitivity, and off-site reading of the EEG record are possible. cEEG is recorded digitally to storage media with standard or small-footpoint EEG recording devices. For most NICU applications, recording rates of 128-256 samples/s/channel provide adequate resolution for reliable interpretation.[4] The recording is done using 21 electrodes placed according to the International 10-20 System. In view of the high level of 60-Hz background activity in the ICU, it is advisable to record or at least display EEG with a 60-Hz notch filter in place. Recording synchronized video with EEG is essential for maximizing the efficiency and accuracy of cEEG interpretation. The role of the EEG technologist is particularly important in these patients to aid in recognizing and minimizing artifact, to enhance communication between electroencephalographers and clinicians, to assess the effect of alerting stimuli, and to note possible subtle clinical correlates of electrographic seizures. Some centers use quantitative EEG (QEEG) tools such as compressed spectral array (CSA). Use of CSA can allow visualization of prolonged trends that are difficult to appreciate on raw EEG. CSA data helps in assessing the progression of the cause of NCSE.

The problems associated with long-term EEG recordings in the NICU include: (1) faulty electrodes, either single- or multiple-scalp electrodes or ground or reference electrodes; (2) connections of electronic equipment; (3) induced artifacts from electronic devices and non-electronic equipment; (4) electrode placement issues; and (5) biological, including movement-related, artifacts. Continuous quality improvement strategies should be implemented to minimize problems. Prompt troubleshooting and regular review sessions are two important components.[15] Maintaining patient-to-EEG interface in obtunded or comatose patients is a major problem. The various approaches practiced include subdural needle electrodes glued to the scalp with collodion, subdural needles stapled to the scalp with surgical staples, and standard disk electrodes glued to the scalp with collodion.[4]

There is no consensus on the time duration of recording to record NCSE electro-clinical correlation. The diagnosis of NCSE is dependent on demonstrating the presence of ongoing seizure activity without convulsive movements. For the diagnosis of NCSE these EEG-ictal episodes should be continuous or recurrent for >30 min without improvement in clinical state or return to preictal EEG pattern between seizures.[1] At times this may require prolonged monitoring. Available evidence suggests that at least 24 hours recording is essential. Seizures were detected within the first 24 hours of cEEG monitoring in 88% of all patients who would eventually have seizures detected by cEEG. In another 5% the first seizure was recorded on monitoring day 2, and in 7% the first seizure was detected after 48 hours of monitoring. Comatose patients were more likely to have their first seizure recorded after >24 hours of monitoring.[7]

NCSE - Diagnosis

In a given clinical setting it is the cognitive or behavioral change from the patient′s baseline (which may be abnormal) that would suggest the possibility of NCSE. However, in patients with mental retardation, encephalopathy, or major psychiatric disease there may be difficulty in identifying what constitutes a change in the baseline status. The lethargy or drowsiness seen in these contexts may mask a non-convulsive state. Diagnosis of NCSE involves the clinical picture of an abnormal mental status with diminished responsiveness, a supportive EEG, and often responsiveness to benzodiazepine administration. The diagnosis may be difficult in two situations. First, if the patient is comatose and has another reason for encephalopathy, then even if seizure activity stops, coma may continue so a clinical response to benzodiazepines is not a reliable indicator. Secondly, the EEG pattern may not be highly rhythmic or epileptiform. If there is an equivocal response to benzodiazepines in the latter case, then the diagnosis cannot be established entirely from the EEG and other clinical factors must be used to establish the diagnosis.[1]

An emerging unifying hypothesis of NCSE has been to divide NCSE based on presence of a primary epileptic encephalopathy in which mental status changes are due to seizure activity or electrographic NCSE in which the electrographic pattern of NCSE is present but encephalopathy is most likely due to some other brain insult.[2] Kaplan[1] developed a more detailed classification utilizing clinical characteristics to categorize patients, especially mental status (1) localization-related NCSE, (2) generalized NCSE (GNSE), and (3) indeterminate or intermediate NCSE. GNSE is further divided into: (1) Absence status epilepticus (ASE) associated with childhood absences or rarely with juvenile myoclonic epilepsy (JME), (2) patients with childhood onset, secondary generalized epilepsy, often with mental retardation, often with greater confusion and myoclonus; (3) elderly patients without epilepsy who present de novo, usually with toxic or metabolic dysfunction, intake of psychotropic drugs or benzodiazepine withdrawal, and (4) generalized non-convulsive status secondary to partial epileptic status of temporal or frontal lobe origin. Recently, Shneker and Fountain[16] categorized patients based on the easily observable characteristics of etiology, mental status, and presence of complications, thus relying less on the interpretation necessary for traditional classification. Such an approach helps the clinician to predict the probable outcome in a particular clinical setting and also to decide the appropriate therapeutic options.

Electrographic Seizures or NCSzs - Diagnostic EEG Criteria

Young et al[17] proposed primary and secondary criteria for an electrographic seizure or a NCSz [Table - 1]. To qualify, at least one of the primary criteria and one or more of the secondary criteria, with discharges of >10 sec are required. For the diagnosis of NSCE these EEG-ictal episodes should be continuous or recurrent for >30 min without improvement in clinical state or return to preictal EEG pattern between seizures.

Litt et al[18] defined electrographic seizures as distinct discharges that evolve over time with a change in the frequency, amplitude, and distribution and described three EEG patterns of electrographic SE: focal, [Figure - 1] generalized, and bihemispheric. With these criteria it is relatively easy to diagnose NCSE when there are frequent electrographic seizures, particularly when they are focal. However, with regard to generalized discharges, there are serious limitations, as the authors did not include invariant spike-and-wave discharges; there was usually a waxing and waning of these patterns for inclusion. This can often be a very subjective interpretation.

NCSzs - EEG Characteristics

EEG characteristics of NCSzs/NCSE are heterogeneous. Morphology is highly variable and includes typical spike-wave (TSW) discharges, atypical spike-wave (ATSW) [Figure - 2] and [Figure - 3] multiple or polyspike wave discharges (MSW) [Figure - 4], and rhythmic delta activity with intermixed spikes (RDIS) [Table - 2]. The morphology of the ictal discharges may vary during the course of a single EEG. Discharge frequency may be between 1 to 3.5 Hz and only a small proportion (4%) may have 3 Hz or faster frequencies.[16],[18],[19] NCSE can be classified on EEG grounds as generalized, focal, or generalized with a focal emphasis.[19]

Periodic epileptiform discharges (PED), periodic lateralized epileptiform discharges (PLED), generalized PED (GPED), bilateral independent PLED (BiPLED), triphasic waves, frontal intermittent rhythmic delta activity, and suppression-burst activity are frequently seen in patients with seizures on cEEG monitoring [Table - 2]. However, many of these are controversial, particularly as to whether they are ictal.[7],[20] PLEDs are seen frequently in the aftermath of SE[21],[22] and have been associated with poor outcome.[23],[24]

The frequency of various ictal discharges was variable in different studies. In the series by Granner and Lee[19] ictal discharges were generalized (TSW: 7%; ASW; 53%; MSW: 20%; RDIS: 20%) in 69%, diffuse with focal (ASW: 53%; RDIS: 47%) predominance in 18%, and focal (ASW: 64%; MSW: 9%; RDIS: 27%) in 11%. In this study the morphologies and patterns and persistence varied greatly. Young et al[17] reported repetitive focal spikes or sharp waves showing variable spread in 57%; generalized polyspikes or polyspike-wave with focal onset or accentuation in 16%, generalized sharp waves or generalized sharp- or slow-waves complexes < 3 Hz in 10%, focal rhythmic waves with intermittent spikes in 8%, lateralized spikes or sharp waves in 4%, rhythmic waves of varying amplitude and frequency in 2%, and generalized polyspikes and waves in 2% patients. In another study the discharges were generalized in 59% and lateralized or localized in 41%.[16] Thus the EEGs in a wide variety of cases of NCSE share three typical features: (1) epileptiform spike or sharp wave discharges or very rhythmic slowing with sharp features; (2) rhythmicity; and (3) recurrence frequencies of > 1 Hz.

Certain EEG patterns are more commonly associated with the underlying etiology. Spike-wave (whether or not generalized) and generalized EEG discharges were much more likely to be seen in the epilepsy group than in patients with NCSE due to acute medical illness.[16]

cEEG Monitoring - When?

Available evidence indicates that NCSzs and NCSE probably occur in a substantial fraction of obtunded or unresponsive patients, 11-56% in NICU settings.[4],[7],[25] In a recent hospital-based retrospective study of cEEG, electrographic seizures were associated with coma; age <18 years, a history of epilepsy, and convulsive seizures during the current illness prior to monitoring.[7] In the same study, of the 105 patients with unexplained decrease in the level of consciousness as the primary diagnosis, NCSzs were recorded in 16 (16%), 5 (31%) of them had NCSE.

Electrographic seizures may persist after convulsive SE. Of the 180 patients who were monitored after clinical status epilepticus, 96 had ictal discharges, which included both NCSzs and NCSE.[23] In another study cEEG monitoring demonstrated electrographic seizures in 48% of patients and 14% manifested NCSE.[11] The present evidence suggests that electrographic burst suppression is superior to the control of clinical and electrographic seizures activity.[26]

cEEG monitoring detected NCSz/NCSE in 28% of patients with intracerebral hemorrhage (ICH) and in 6% of patients with ischemic stroke. In patients with ICH, cEEG detected four times as many electrographic seizures as occurred clinically and seizures were associated with progressive midline shift and also worsening neurological function.[27] cEEG monitoring detected NCSE for 8% of patients with subarachnoid hemorrhage and otherwise unexplained coma or neurological deterioration. The seizures were highly refractory to therapy, and the prognosis for these patients was extremely poor.[28]

Use of cEEG in patients with traumatic brain injury demonstrated that convulsive and non-convulsive seizures occured in 22% of patients, with six of them displaying SE. In more than half of the patients (52%) the seizures were non-convulsive and were diagnosed on the basis of EEG studies alone.[29]

Based on the above data the possible clinical settings for cEEG to detect NCSE can be the following:

• Patient with impaired consciousness due to acute brain injury due to any cause
• Patients with unexplained impaired consciousness
• Patients with convulsive SE not awake following treatment
• Patients with refractory SE

Diagnosis of NCSE - The Impact

The potential impact of early diagnosis of NCSE will be on the treatment and the outcomes. Duration of ictal activity and the time delay to diagnosis are independent predictors of outcome. When the NCSE duration was less than 10 hours, 60% of patients returned home and 10% died, whereas when the NCSE duration was more than 20 hours none returned and 85% died. This was independent of etiology. With regard to delayed diagnosis, when the NCSE was diagnosed in less than 30 minutes, 36% died and when the NCSE was diagnosed after more than 24 hours, 75% died.[16]

Mortalities were higher in acute symptomatic NCSE (27%) vs. the epilepsy-related (3%) and cryptogenic NCSE (18%). Similarly, mortalities were higher in patients with severe mental status impairment (39%) when compared to those with mild impairment (7%).[19] This data from cEEG monitoring with regard to NCSE has an impact on treatment strategies. Patients with epilepsy as the only cause of NCSE should probably not be routinely treated very aggressively. The rationale is that they are unlikely to die from NCSE. Patients with NCSE of cryptogenic etiologies should be treated aggressively. If NCSE is due to an acute medical illness, treatment should be aggressive and pentobarbital, propofol, or midazolam are the drugs of choice. Electrographic seizures and occasional short-lasting NCSzs may not require any specific treatment. However, it is our policy to treat NCSz clusters.

In conclusion, NCSzs/NCSE probably occur in a substantial fraction of obtunded or unresponsive patients. NCSz semiology is too subtle clinically to be noticed. Most often, mental status impairment is the presenting feature. Duration of ictal activity and the time delay to diagnosis are independent predictors of outcome. cEEG monitoring allows the detection of changes in the function of the thalamocortical system at a reversible stage, often when there are no clinical indications of such phenomena. This makes cEEG an excellent method for supplementing single or serial recordings in the detection and management of NCSzs/NCSE.

REFERENCES

1.	Kaplan PW. Nonconvulsive status epilepticus. Seminars in Neurology 1996;16:33-40.  Back to cited text no. 1  [PUBMED]
2.	Murthy JMK. Nonconvulsive status epilepticus: An under diagnosed and potentially treatable condition. Neurol India 2003;51:453-4.  Back to cited text no. 2
3.	Jordan KG. Continuous EEG and evoked potential monitoring in the neuroscience intensive care unit. J Clin Neurophysiol 1993;10:445-75.  Back to cited text no. 3  [PUBMED]
4.	Scheuer MJ. Continuous EEG monitoring in the intensive care unit. Epilepsia 2002;43:114-27.  Back to cited text no. 4
5.	Jordan KG. Nonconvulsive seizures (NCS) and nonconvulsive statue epilepticus (NCSE) detected by continuous monitoring in the Neuro-ICU (NICU-CEEG) (Abstract). Neurology 1992;42:180.  Back to cited text no. 5
6.	Privitera MD, Strawsurg RH. Electroencephalographic monitoring in the emergency department. Emerg Med Clinics North Am 1994;12:1089-101.  Back to cited text no. 6
7.	Claassen J, Mayer SA, Kowalski RG, Emerson RG, Hirsch LJ. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 2004;62:1743-8.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.	Towne AR, Waterhouse EJ, Morton LD, Kopee GL, Brown AJ, DeLorenzo RJ. Unrecognized nonconvulsive status epilepticus in comatose patients (Abstract). Epilepsia 1998;39:K07.  Back to cited text no. 8
9.	Celesia GG, Modern concepts of status epilepticus. JAMA 1976;235:1571-4.  Back to cited text no. 9
10.	Dunne JW, Summers QA, Stewart-Wyne EG. Nonconvulsive status epilepticus: A prospective study in adult general hospital. Q J Med 1987;23:117-26.  Back to cited text no. 10
11.	DeLorenzo RJ, Waterhouse EJ, Towne AR, Boggs JG, Ko D, DeLorenzo GA, et al. Persistent nonconvulsive status epilepticus after control of convulsive status epilepticus. Epilepsia 1998;38:833-40.  Back to cited text no. 11
12.	Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan JA, et al. A comparison of four treatments for generalized convulsive status epilepticus, Veteran Affairs Status Epilepticus Cooperative Study Group. N Engl J Med 1998;339:792-8.  Back to cited text no. 12
13.	Towne AR, Waterhouse EJ, Boggs JG, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 2000;54:340-5.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.	Fountain NB, Waldman W. Effects of benzodiazepines on triphaic waves - implications for nonconvulsive status epilepticus. J Clin Neurophysiol 2001;18:345-53.  Back to cited text no. 14
15.	Young GB, Campbell VC. EEG monitoring in the intensive care unit: Pitfalls and caveats. J Clin Neurophysiol 1999;16:40-5.  Back to cited text no. 15  [PUBMED]
16.	Shneker BF, Foutain NB. Assessment of acute morbidity and mortality in nonconvulsive status epilepticus. Neurology 2003;61:1066-173.  Back to cited text no. 16
17.	Young GB, Jordan KG, Doig GS. An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: An investigation of variables associated with mortality. Neurology 1996;47:83-9.  Back to cited text no. 17  [PUBMED]
18.	Litt B, Wityk RJ, Hertz SH, Mullen PD, Weiss H, Ryan DD, et al. Nonconvulsive status epilepticus in the critically ill elderly. Epilepsia 1998;39:1194-202.  Back to cited text no. 18  [PUBMED]
19.	Granner MA, Lee SI. Nonconvulsive status epilepticus: EEG analysis in a large series. Epilepsia 1994;35:42-7.  Back to cited text no. 19  [PUBMED]
20.	Brenner RP. Is it status? Epilepsia 2002;43:103-13.  Back to cited text no. 20  [PUBMED]
21.	Treiman DM. Electroclinical features of status epilepticus. J Clin Neurophysiol 1995;12:343-52.  Back to cited text no. 21
22.	Garzon E, Fernandes RM, Sakamoto AC. Serial EEG during human status epilepticus: Evidence for PLED as an ictal pattern. Neurology 2001;57:1175-88.  Back to cited text no. 22
23.	Jaitly R, Sgro JA, Towne AT, Ko D, De Lorenzo RJ. Prognostic value of EEG monitoring after status epilepticus: A prospective adult study. J Clin Neurophysiol 1997;14:326-34.  Back to cited text no. 23
24.	Nei M, Lee J-M, Shanker VL, Sperling MR. The EEG and prognosis in status epilepticus. Epilepsia 1999;40:157-63.  Back to cited text no. 24
25.	Haffey S, McKernan A, Pang K. Nonconvulsive status epilepticus: A profile of patients diagnosed within a tertiary referral center. J Neurol Neurosurg Psychiatry 2004;75:1043-4.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]
26.	Claassen J, Hirsch LJ, Emerson GR. Mayer SA. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: A systemic review. Epilepsia 2002;43:146-53.  Back to cited text no. 26
27.	Vespa PM, O'Phelan K, Shah M, Mirabelli J, Starkman S, Kidwell C, et al. Acute seizures after intracerebral hemorrhage: A factor in progressive midline shift and outcome. Neurology 2003;60:1441-6.  Back to cited text no. 27
28.	Dennis LJ, Claassen J, Hirsch LJ, Emerson RG, Connolly ES, Mayer SA. Nonconvulsive status epilepticus after subarchnoid hemorrhage. Neurosurgery 2002;51:1136-43.  Back to cited text no. 28  [PUBMED]  [FULLTEXT]
29.	Vespa PM, Nuwer MR, Neonov V, Ronne-Engstom E, Hovda DA, Bergsneider M, et al. Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous EEG in the intensive care unit. J Neurosurg 1999;91:750-60.  Back to cited text no. 29

Copyright 2004 - Neurology India

Neurology India, Vol. 52, No. 4, October-December, 2004, pp. 436-438

Original Article

Variability in the extent of sensory deficit after sural nerve biopsy

Kumar Sudhir, Jacob J

Neurology Unit, Department of Neurological Sciences, Christian Medical College, Vellore - 632 004
Correspondence Address:Department of Neurological Sciences, Christian Medical College Hospital, Vellore - 632004, Tamilnadu, drsudhirkumar@yahoo.com

Code Number: ni04149

ABSTRACT

Key Words: Sural nerve biopsy, Complications, Sensory deficit, Variations

INTRODUCTION

Sural nerve biopsy (SNBx) is one of the most common procedures employed in the evaluation of peripheral nerve disorders. It is particularly useful in establishing the diagnosis of certain neuropathies like leprosy, vasculitic neuropathy, amyloid neuropathy, sarcoid neuropathy, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).[1] In about two-thirds of the patients the results of SNBx are likely to alter the management.[2] However, the procedure is associated with a number of complications such as persistent sensory loss, pain and paresthesia in the territory of the sural nerve, painful neuromas, and infection at the biopsy site.[2],[3],[4],[5],[6] The extent of sensory deficit (Sdef) following SNBx varies widely. Therefore, it is prudent to balance the diagnostic yield of SNBx against the complications, so that a better informed consent can be obtained from patients.

MATERIALS AND METHODS

This prospective study was conducted in the Neurology Department of a tertiary teaching hospital. All consecutive inpatients admitted between May 2003 and March 2004 who had an SNBx were eligible for inclusion. However, patients with evidence of Sdef prior to the procedure or with abnormal sural nerve amplitude were excluded. Informed consent was obtained from all the patients.

Technique of SNBx: The sural nerve was exposed after making an incision midway between the lateral malleolus and tendoachilles. Whole sural nerve biopsy was performed and a 3 cm segment of the nerve was excised. Severed ends of the nerve were not sutured.[7] The procedure was done under local anesthesia.

Sensory Assessment: Detailed sensory testing for touch, pain, temperature, vibration and joint-position was performed between the 7^th and 14^th days after the procedure. Touch was tested using a wisp of cotton, pain using a sharp pin, temperature using test tubes filled with hot or cold water, and vibration was tested with a 128-Hz tuning fork.[8] Sdef was considered to be present if there was absence or reduced perception of any of the modalities tested. Sensory assessment was also performed on the normal side (the non-biopsied side). The sensory assessment was repeated after three months or later. Even though the authors were part of the treating team, which decided to perform SNBx, they however had no direct influence on the decision.

RESULTS

A total of 50 patients (26 women) fulfilled the inclusion and exclusion criteria. The mean age was 37.4 years (16-63 years). Pre-biopsy diagnosis included vasculitis (36 patients), leprosy (10 patients), and CIDP (8 patients) (some patients had more than one indication). The duration of symptoms ranged from five days to seven years (mean 11 months). Findings obtained on nerve conduction studies are summarized in [Table - 1]. All the patients had normal sural nerve conductions and none had any sensory deficit in the territory of the sural nerve prior to the procedure. Biopsy was performed on the left side in 40 patients and on the right side in 10.

Extent of Sdef: Sdef along the lateral aspect of the foot was present in 46 (92%) patients. Sdef over the dorsal aspect of the toes varied widely [Table - 2]. Forty-eight patients (96%) had Sdef extending beyond the outer aspect of the small toe.

Other complications: Postoperative pain was present in 21(42%), and paresthesia in 18 (36%) patients. Infection at the biopsy site was noted in four (8%).

Yield of nerve biopsy: SNBx yielded a definitive diagnosis in 17 (34%) patients [Table - 3]. Of the remaining 33 patients with normal findings on SNBx, the procedure was helpful in excluding vasculitis in 24 patients (final diagnosis in them included acute disseminated encephalomyelitis (ADEM) in 12, multiple cerebral infarcts in 10, isolated central nervous system angiitis and central nervous system lupus in one each) [Table - 3]. Thus, SNBx played an important role in the management of 41 (82%) patients. There was no correlation between the etiology or the extent of neuropathy and the complication rate.

Follow-up: A total of 36 patients were seen at intervals ranging from 3-10 months (mean 6.3 months) after the procedure. Sdef was present in 32 (89%) and paresthesia in 14 (39%) patients. The wound had healed in two of these patients who initially had infection of the biopsy site. Fourteen (39%) patients had persistent pain in the sural nerve territory. None of the patients had any impairment in the activities of daily living or ever consulted a physician for these symptoms.

DISCUSSION

Sural nerve biopsy is an established procedure employed for evaluating peripheral neuropathy. Notwithstanding the usefulness of SNBx in the diagnostic evaluation and management of patients with peripheral neuropathy, this procedure is associated with several complications. These include persistent pain (67%),[2] dysesthesia, paresthesia, and sensory deficit in the sural nerve territory, neuroma formation at the severed end of the nerve and infection (10-15%)[2],[4] at the biopsy site. These symptoms may persist for many months; 33% out of 54 patients reported paresthesias and 19% had dysesthesias after a follow-up of 5-32 months.[9] Sensory deficit after SNBx is another major problem, as noted in 93% of the patients in two studies.[3],[9] The follow-up period in these two studies was 21 and 5-32 months respectively. In our study, 89% had sensory deficit at a mean follow-up period of six months; however, our patients demonstrated a great variability in the extent of Sdef. The most consistent area of Sdef was the lateral aspect of the foot, in 92% of patients. Sdef over the dorsal aspect of the toes was present in all, however, it ranged from only the outer aspect of the 5th toe to three and a half toes (3rd to 5th toes and outer aspect of the 2nd toe) [Table - 1]. The union of the medial and lateral sural cutaneous nerves forms the sural nerve. Though this union occurs at various sites, the commonest site is the lower third of the leg.[10]

In the dorsum of the feet, communications may be noted between the branches of the dorsal sural nerve and the lateral branches of the distal superficial peroneal nerve. Typically, the superficial peroneal nerve is believed to supply the dorsal skin of all toes, except the lateral side of the 5th toe (supplied by the sural nerve) and the adjoining sides of the great and 2nd toes (supplied by the deep peroneal nerve).[11] However, in our series, 96% of the patients had Sdef extending beyond the typical distribution of the sural nerve (outer aspect of the 5th toe). Our study is probably the first prospective study that evaluated the variability in Sdef following SNBx.

All the studies including the present study demonstrate a significant, often persistent Sdef after SNBx. Some studies studied the possible associated factors that may predispose the patients to develop sensory deficit following SNBx: (i) Diabetes Mellitus: In a prospective study, the extent of Sdef at 6, 12, or 18 months did not differ between patients with and without diabetes mellitus.[12] However, in another study, mild persistent sensory symptoms were significantly more common in patients with diabetes mellitus (64%) when compared to patients without diabetes mellitus (28%). The follow-up period was about six years.[13] These symptoms, however, did not interfere with the activities of daily living or warrant any medical therapy. In our series, only three patients had diabetes, and the Sdef was confined to the outer aspect of the 5th toe in two and to both sides of the 5th toe in one. (ii) Sural Nerve Action Potentials (SNAPs) prior to SNBx: It was reported that patients with detectable SNAPs were twice as likely to develop a new numbness as compared to those with absent SNAPs.[2] However, in another study, the diagnostic yield of SNBx increased in patients with a greater reduction in motor conduction velocities.[14] (iii) Length of the nerve excised: No correlation was observed between the length of the nerve excised and the complication rate.[4] (iv) Fascicular versus whole sural nerve biopsy: Pollock et al reported no significant difference in areas of sural sensory loss between fascicular and whole nerve biopsy groups.[15] The possible reasons include (1) cutting interfascicular branches during the 3-5 cm fascicular dissection may cause more extensive damage to the sural nerve than would be anticipated from the number of fascicles removed and (2) the blood supply to intact fascicles might be compromised by damage to the vasa nervorum. Whole nerve biopsy for sural nerve, therefore, is recommended as it is simpler, has greater diagnostic potential, and allows for a more complete morphological evaluation without increasing the complication rate.

It is clear from the foregoing discussion that the Sdef after SNBx is inevitable and no factor seems to alter the extent or rate of this complication. Therefore, the current interest has shifted to post-biopsy care. Schoeller et al recently reported the benefits of microsurgical repair of the sural nerve after nerve biopsy.[16] This procedure involves careful mobilization of the proximal and distal nerve stumps after resecting a 10-mm segment of the sural nerve under local anesthesia, and uniting with epineural suture techniques, under a surgical microscope. A return of sensations in the sural nerve territory to the pre-biopsy level was noted as early as six months after the microsurgical repair. It should be mentioned here that this technique is in a preliminary stage and further studies are needed before a final recommendation can be made.

Patients included in our study had normal sensations in the sural nerve territory and normal sural nerve conductions. This is quite different from the routine clinical situation, where most of the patients undergoing SNBx biopsy have significant neuropathy, clinically or electrophysiologically or both. In fact, during our study period, 81 such patients were excluded. Therefore, data obtained from this study cannot be generalized to all patients undergoing SNBx.

In summary, SNBx leads to Sdef in the sural nerve territory in almost all the patients, which persists for many years. Our study has shown that the extent of Sdef is highly variable and 96% of patients have deficits beyond the region of the classical sural nerve distribution (outer aspect of the little toe). It is important to inform about the possibility of a more extensive Sdef to the patients prior to the SNBx to avoid dissatisfaction later. The encouraging fact for us, however, is that the post-biopsy complaints are mild and almost never interfere with the activities of daily living.

REFERENCES

Copyright 2004 - Neurology India

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