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  • Review
  • Open Access

Preliminary guideline- and pathophysiology-based protocols for neurocritical care

Journal of Intensive Care20186:45

https://doi.org/10.1186/s40560-018-0316-6

  • Received: 12 April 2018
  • Accepted: 27 July 2018
  • Published:

Abstract

Background

Because of the complex pathophysiological processes involved, neurocritical care has been driven by anecdotal experience and physician preferences, which has led to care variation worldwide. Standardization of practice has improved outcomes for many of the critical conditions encountered in the intensive care unit.

Main body

In this review article, we introduce preliminary guideline- and pathophysiology-based protocols for (1) prompt shivering management, (2) traumatic brain injury and intracranial pressure management, (3) neurological prognostication after cardiac arrest, (4) delayed cerebral ischemia after subarachnoid hemorrhage, (5) nonconvulsive status epilepticus, and (6) acute or subacute psychosis and seizure.

Conclusion

These tentative protocols may be useful tools for bedside clinicians who need to provide consistent, standardized care in a dynamic clinical environment. Because most of the contents of presented protocol are not supported by evidence, they should be validated in a prospective controlled study in future. We suggest that these protocols should be regarded as drafts to be tailored to the systems, environments, and clinician preferences in each institution.

Keywords

  • Neurocritical care
  • Protocols
  • Guidelines
  • Pathophysiology
  • Shivering
  • Neurological prognostication
  • Delayed cerebral ischemia
  • Nonconvulsive status epilepticus
  • Psychosis
  • Seizure

Background

The art of neurocritical care requires an understanding of the pathophysiology of the highly complex central nervous system. Because of its complexity and the lack of evidence, the approach to neurocritical care is often clinician-dependent, i.e., driven by anecdotal experience and physician preferences, which leads to care variation. Overall, standardization of practice has improved outcomes for many critical conditions in the intensive care unit; thus, greater emphasis should be placed on reducing variation in neurocritical care practice.

Guideline- and pathophysiology-based protocols are concise yet comprehensive and are useful for bedside clinicians who need to provide consistent, standardized practice in a dynamic clinical environment. We introduce five preliminary protocols in this article. Because most of the text of the protocols addresses management in neurocritical care fields that lack firm evidence, and because of the varied availability of medical resources among institutions, we recommend that these protocols be used as drafts to be customized for the systems, environments, and clinical preferences of each institution.

Protocols

Prompt shivering management (Fig. 1)

Shivering is a physiological homeostatic response to maintain or raise temperature in hypothermia or fever when the set point temperature is elevated. However, shivering counteracts the effort of fever management and targeted temperature management (TTM)/therapeutic hypothermia, which are critical interventions to mitigate secondary brain injury. With inadequate shivering management, target temperature is difficult to achieve in a timely manner and may potentially worsen outcome. Furthermore, shivering increases the cerebral metabolic rate and may result in increased intracranial pressure (ICP) and brain oxygen consumption [1, 2]. Lastly, shivering increases the total body metabolic rate and total CO2 production, which may raise the partial pressure of CO2 and raise ICP. Therefore, shivering should be regarded as a neurological emergency requiring immediate control in patients with acute brain injury, and any protocol for shivering management should encourage clinicians to expedite treatment. The present draft proposal for shivering management refers to the Bedside Shivering Assessment Scale and shivering protocol proposed by Badjatia and Brophy, respectively, [1, 2] and was refined, based on our practice, to achieve prompt shivering control (Fig. 1).
Fig. 1
Fig. 1

Preliminary protocol for prompt shivering management [1, 2]. Modified from Brophy [2] with permission. Abbreviations: BSAS Bedside Shivering Assessment Scale, ECG electrocardiogram, IV intravenously, PO per oral, H hour, min minute

Traumatic brain injury and ICP management (Fig. 2)

Intracranial hypertension, commonly defined as persistent elevation of ICP above 20–22 mmHg, is a relatively common neurologic complication seen after traumatic brain injury (TBI). If untreated, it can lead to cerebral ischemia, brain herniation, and possibly brain death. Therefore, care providers must promptly recognize the early clinical and radiographic features of elevated ICP and aggressively treat with a goal of reducing mortality and morbidity. The adult brain is a nearly incompressible substance enclosed in a fixed cranium. Therefore, ICP will inevitably be affected by a volume change in any of the three main intracranial components—cerebrospinal fluid (CSF), brain parenchyma, and blood [3]. In addition, if there is a new space-occupying lesion within the fixed cranium (i.e., hematoma), it will inevitably increase ICP. When assessing a patient with elevated ICP, it is important to determine whether the contributing factor is a focal, global, or mixed process since the treatment strategy may be different for each type of mass effect. If there is a focal, new mass-occupying lesion that is causing a regional mass effect and brain tissue compression, the first step is to consider surgical evacuation. Once the focal mass effect is ruled out or treated, global elevation of ICP must be addressed. The overarching strategy to control globally elevated ICP is to (1) optimize cerebral perfusion, oxygenation, and venous drainage; (2) prevent fever, hypercapnia, hyponatremia, hypo/hyperglycemia, and seizure; (3) provide adequate cerebral metabolic suppression with sedation; and (4) reduce cerebral edema with osmotic therapy. For refractory intracranial hypertension, treatments to be considered include pentobarbital-induced coma, therapeutic hypothermia, ventriculostomy placement for CSF diversion, and decompressive craniectomy. Ideally, a protocol for TBI management should include not only ICP control but also indications of initial surgical intervention for intracranial hematoma and basic management to prevent secondary brain injury. Step 1 (indications for surgical intervention) of the preliminary protocol is based on the recommendations by Bullock et al. [47], and step 2 (indications for ICP monitoring) and step 3 (basic management of TBI and ICP control) were developed in accordance with the guidelines for management of severe traumatic brain injury of the Brain Trauma Foundation and our practice (Fig. 2) [8].
Fig. 2
Fig. 2

Preliminary protocol for traumatic brain injury and ICP management [48]. Abbreviations: CT computed tomography, SBP systolic blood pressure, U units, 3PCC 3-factor prothrombin complex concentrate, 4PCC 4-factor prothrombin complex concentrate, ICP intracranial pressure, CVP central venous pressure, PCWP pulmonary capillary wedge pressure, SaO2 arterial oxygen saturation, PaO2 arterial pressure of oxygen, PaCO2 arterial pressure of carbon dioxide

Neurological prognostication after cardiac arrest (Fig. 3)

Cardiac arrest causes complete cessation of cerebral perfusion and rapidly depletes oxygen and glucose delivery to cerebral tissue. Cell death, which includes ion channel dysfunction and cell membrane destabilization, release of destructive enzymes, cell swelling, and, eventually, apoptosis, can begin within 5 min after complete cessation of cerebral perfusion [911]. After return of spontaneous circulation, neurological prognostication is essential because it enables clinicians to provide information to family members or surrogates who must consider decisions to limit care for patients with little hope of meaningful neurological recovery [11]. To date, there is no definitive diagnostic test to accurately predict functional outcome after cardiac arrest. Moreover, clinical findings shortly after cardiac arrest have little relationship to patient outcomes [12]. However, the use of a systematic approach allows for reliable prediction of a very poor neurological outcome (persistent vegetative state) and provides family members and surrogates with the information necessary to make decisions [1316]. A protocol that clearly addresses “what to do next” would be helpful for clinicians. The present preliminary protocol is based on the 2015 European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care [13], but includes additional detailed stepwise instructions (Fig. 3).
Fig. 3
Fig. 3

Preliminary protocol for neurological prognostication after cardiac arrest [13, 16]. Modified from Nolan [13] with permission. Abbreviations: ROSC return of spontaneous circulation, EEG electroencephalography

Delayed cerebral ischemia after subarachnoid hemorrhage (Fig. 4)

After subarachnoid hemorrhage, notably from a ruptured cerebral aneurysm, cerebral vasospasm can develop, thus leading to delayed cerebral ischemia (DCI) and possibly infarction. The mechanism of DCI is complex and is not solely attributed to large-vessel narrowing and associated low blood flow distally [17, 18]. Other postulated mechanisms are early brain injury, microcirculatory dysfunction with loss of cerebral autoregulation, cortical spreading depolarization, and microthrombosis [19, 20]. A DCI diagnosis is made clinically on the basis of symptoms such as new changes in mental status and neurologic deficits. Additional relevant information includes findings of CT or MRI angiography, digital subtraction angiography, and transcranial Doppler (TCD) ultrasound. In addition, other reversible causes of neurological changes must be ruled out, such as delayed hydrocephalus, nonconvulsive seizure, rebleeding, toxic-metabolic encephalopathy from infection, and medication side effects. To date, nimodipine, a calcium-channel blocker with cerebral vasodilatory effect, is the only drug that has been shown to improve neurological outcomes in patients with subarachnoid hemorrhage [21]. Other calcium-channel blockers, such as nicardipine, have been used in countries where nimodipine is unavailable [22] but have not been shown to improve outcomes. Hemodynamic augmentation to increase oxygen delivery to the brain, including volume optimization and induced hypertension, is the mainstay for management of new-onset DCI. For refractory cases where medical management is ineffective, intra-arterial interventions such as balloon angioplasty and intra-arterial administration of calcium-channel blockers are a second-line treatment [23]. A protocol should include risk stratification and stepwise treatment for DCI in individual patients. The present preliminary protocol describes basic management of subarachnoid hemorrhage and risk stratification and monitoring, based on our practice and the existing literature [2426]. Diagnosis and management of DCI are based on recommendations from the neurocritical care society and our practice [23] (Fig. 4).
Fig. 4
Fig. 4

Preliminary protocol for monitoring and diagnosis of delayed cerebral ischemia after subarachnoid hemorrhage [23, 24]. Abbreviations: SAH subarachnoid hemorrhage, DVT deep vein thrombosis, IVH intraventricular hemorrhage

Diagnosis of nonconvulsive status epilepticus (Fig. 5)

Nonconvulsive status epilepticus (NCSE) is characterized by electrographic seizure activity without clinical convulsions in patients who do not fully recover consciousness between attacks [27]. Although the impact of treating NCSE on clinical outcomes has not been investigated in a randomized controlled trial, the prognosis of NCSE is believed to be poor if not treated since untreated seizure is associated with secondary brain injury [2830]. A diagnosis of NCSE should be considered in any patient with discrepancies between his/her neurological findings and clinical history or imaging findings such as CT or MRI. The typical example is a patient who develops sudden unexpected neurological deterioration after successful management of a structural brain injury without new findings on CT or MRI. Although the condition is referred to as nonconvulsive, patients with NCSE may have subtle motor symptoms such as sustained eye deviation, nystagmus, lip smacking, and twitching in the face or extremities [31]. Definitive diagnosis requires electroencephalography (EEG), and continuous EEG monitoring increases the sensitivity and specificity of NCSE diagnosis. We attempted to develop an algorithmic protocol to interpret EEG and diagnose NCSE for bedside clinical use. Based on the current guidelines [27, 32], this draft protocol for diagnosis of NCSE is designed to simplify NCSE diagnosis and management (Fig. 5).
Fig. 5
Fig. 5

Preliminary protocol for diagnosis of nonconvulsive status epilepticus [32]. Abbreviations: AED anti-epileptic drug

Acute or subacute psychosis and seizure (Fig. 6)

Many medical conditions and pharmacologic side effects can cause unexpected psychosis or seizure. However, some treatable and reversible conditions, such as viral encephalitis and autoimmune encephalitis, are frequently missed. Delays in diagnosis and treatment of encephalitis may result in poor neurological outcomes. It is essential to review all possible causes of unexpected psychosis and seizure and to start empirical treatment for a potentially treatable condition before obtaining all examination results. The present draft protocol for diagnosis and management of autoimmune encephalitis includes comprehensive differential diagnoses and algorithms for diagnostic evaluation and was developed on the basis of a comprehensive literature review by Francesc et al., antibody prevalence in epilepsy (APE) score [33], and empirical treatment for autoimmune encephalitis in cases of unexpected psychosis or seizure, as reflected by the expert opinions of the European Federation of the Neurological Societies (EFNS) task force [34] and our practice (Fig. 6).
Fig. 6
Fig. 6

Preliminary protocol for acute or subacute psychosis and newly onset seizure [33, 35]. Modified from Dubey [33] with permission. Abbreviations: VDRL venereal disease research laboratory, HSV herpes simplex virus, VZV varicella zoster virus, HIV human immunodeficiency virus, CMV cytomegalovirus, Anti-TPO anti-thyroid peroxidase, ANA anti-nuclear antibody, ANCA antineutrophil cytoplasmic antibody

Conclusion

The present guideline- and pathophysiology-based protocols that can be customized for particular clinical environments may help providing consistent, standardized care in neurocritical care. Because most of the contents of presented protocol are not supported by evidence, they should be validated in a prospective controlled study in future.

Abbreviations

CSF: 

Cerebrospinal fluid

DCI: 

Delayed cerebral ischemia

EEG: 

Electroencephalography

ICP: 

Intracranial pressure

NCSE: 

Nonconvulsive status epilepticus

TBI: 

Traumatic brain injury

TCD: 

Transcranial Doppler

TTM: 

Targeted temperature management

Declarations

Author contributions

YN is the guarantor of the manuscript content and protocols. YF and KN substantially contributed to the manuscript and protocols. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable

Consent for publication

Not required

Competing interests

The authors declare that they have no competing interests.

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Authors’ Affiliations

(1)
Department of Emergency and Critical Care Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, 3-4-32 Todaijima, Urayasu Chiba, 2790001, Japan
(2)
Department of Emergency and Critical Care Medicine, St. Marianna University Hospital, 2-16-1, Sugao, Kawasaki Kanagawa, 2168511, Japan
(3)
Department of Medicine, Division of Neurology, John A. Burns School of Medicine University of Hawai`i, 1301 Punchbowl Street, Honolulu, HI 96813, USA

References

  1. Badjatia N, Strongilis E, Gordon E, Prescutti M, Fernandez L, Fernandez A, Buitrago M, Schmidt JM, Ostapkovich ND, Mayer SA. Metabolic impact of shivering during therapeutic temperature modulation: the Bedside Shivering Assessment Scale. Stroke. 2008;39(12):3242–7.View ArticlePubMedGoogle Scholar
  2. Brophy GM, Human T. Pharmacotherapy pearls for emergency neurological life support. Neurocrit Care. 2017;27(Suppl 1):51–73.View ArticlePubMedGoogle Scholar
  3. Fishman RA. Cerebrospinal fluid in diseases of the nervous system. Philadelphia: London: Saunders; 1980.Google Scholar
  4. Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, Servadei F, Walters BC, Wilberger J, Surgical Management of Traumatic Brain Injury Author G. Surgical management of posterior fossa mass lesions. Neurosurgery. 2006;58(3 Suppl):S47–55. discussion Si-ivPubMedGoogle Scholar
  5. Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, Servadei F, Walters BC, Wilberger J, Surgical Management of Traumatic Brain Injury Author G. Surgical management of depressed cranial fractures. Neurosurgery. 2006;58(3 Suppl):S56–60. discussion Si-ivPubMedGoogle Scholar
  6. Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, Servadei F, Walters BC, Wilberger JE, Surgical Management of Traumatic Brain Injury Author G. Surgical management of acute epidural hematomas. Neurosurgery. 2006;58(3 Suppl):S7–15. discussion Si-ivPubMedGoogle Scholar
  7. Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, Servadei F, Walters BC, Wilberger JE, Surgical Management of Traumatic Brain Injury Author G. Surgical management of acute subdural hematomas. Neurosurgery. 2006;58(3 Suppl):S16–24. discussion Si-ivPubMedGoogle Scholar
  8. Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery. 2017;80(1):6–15.PubMedGoogle Scholar
  9. Neumar RW. Molecular mechanisms of ischemic neuronal injury. Ann Emerg Med. 2000;36(5):483–506.View ArticlePubMedGoogle Scholar
  10. Pulsinelli WA, Brierley JB, Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol. 1982;11(5):491–8.View ArticlePubMedGoogle Scholar
  11. Lee K. The neuroICU book. 2nd ed. New York: McGraw-Hill Medical; 2017.Google Scholar
  12. Rittenberger JC, Sangl J, Wheeler M, Guyette FX, Callaway CW. Association between clinical examination and outcome after cardiac arrest. Resuscitation. 2010;81(9):1128–32.View ArticlePubMedPubMed CentralGoogle Scholar
  13. Nolan JP, Soar J, Cariou A, Cronberg T, Moulaert VR, Deakin CD, Bottiger BW, Friberg H, Sunde K, Sandroni C. European Resuscitation Council and European Society of Intensive Care Medicine guidelines for post-resuscitation care 2015: section 5 of the European Resuscitation Council guidelines for resuscitation 2015. Resuscitation. 2015;95:202–22.View ArticlePubMedGoogle Scholar
  14. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S, Quality Standards Subcommittee of the American Academy of N. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 67(2):203–210.Google Scholar
  15. Zandbergen EG, de Haan RJ, Stoutenbeek CP, Koelman JH, Hijdra A. Systematic review of early prediction of poor outcome in anoxic-ischaemic coma. Lancet. 1998;352(9143):1808–12.View ArticlePubMedGoogle Scholar
  16. Rossetti AO, Rabinstein AA, Oddo M. Neurological prognostication of outcome in patients in coma after cardiac arrest. Lancet Neurol. 2016;15(6):597–609.View ArticlePubMedGoogle Scholar
  17. Millikan CH. Cerebral vasospasm and ruptured intracranial aneurysm. Arch Neurol. 1975;32(7):433–49.View ArticlePubMedGoogle Scholar
  18. Etminan N, Vergouwen MD, Ilodigwe D, Macdonald RL. Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab. 2011;31(6):1443–51.View ArticlePubMedPubMed CentralGoogle Scholar
  19. Budohoski KP, Guilfoyle M, Helmy A, Huuskonen T, Czosnyka M, Kirollos R, Menon DK, Pickard JD, Kirkpatrick PJ. The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2014;85(12):1343–53.View ArticlePubMedGoogle Scholar
  20. Francoeur CL, Mayer SA. Management of delayed cerebral ischemia after subarachnoid hemorrhage. Crit Care. 2016;20(1):277.View ArticlePubMedPubMed CentralGoogle Scholar
  21. Petruk KC, West M, Mohr G, Weir BK, Benoit BG, Gentili F, Disney LB, Khan MI, Grace M, Holness RO, et al. Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial. J Neurosurg. 1988;68(4):505–17.View ArticlePubMedGoogle Scholar
  22. Tejada JG, Taylor RA, Ugurel MS, Hayakawa M, Lee SK, Chaloupka JC. Safety and feasibility of intra-arterial nicardipine for the treatment of subarachnoid hemorrhage-associated vasospasm: initial clinical experience with high-dose infusions. AJNR Am J Neuroradiol. 2007;28(5):844–8.PubMedGoogle Scholar
  23. Diringer MN, Bleck TP, Claude Hemphill J 3rd, Menon D, Shutter L, Vespa P, Bruder N, Connolly ES Jr, Citerio G, Gress D, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15(2):211–40.View ArticlePubMedGoogle Scholar
  24. Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014;10(1):44–58.View ArticlePubMedGoogle Scholar
  25. Frontera JA, Claassen J, Schmidt JM, Wartenberg KE, Temes R, Connolly ES Jr, MacDonald RL, Mayer SA. Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified fisher scale. Neurosurgery. 2006;59(1):21–7. discussion 21-27View ArticlePubMedGoogle Scholar
  26. de Rooij NK, Greving JP, Rinkel GJ, Frijns CJ. Early prediction of delayed cerebral ischemia after subarachnoid hemorrhage: development and validation of a practical risk chart. Stroke. 2013;44(5):1288–94.View ArticlePubMedGoogle Scholar
  27. Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, Laroche SM, Riviello JJ Jr, Shutter L, Sperling MR, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3–23.View ArticlePubMedGoogle Scholar
  28. Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality in status epilepticus. Epilepsia. 1994;35(1):27–34.View ArticlePubMedGoogle Scholar
  29. DeLorenzo RJ, Garnett LK, Towne AR, Waterhouse EJ, Boggs JG, Morton L, Choudhry MA, Barnes T, Ko D. Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia. 1999;40(2):164–9.View ArticlePubMedGoogle Scholar
  30. Waterhouse EJ, Garnett LK, Towne AR, Morton LD, Barnes T, Ko D, DeLorenzo RJ. Prospective population-based study of intermittent and continuous convulsive status epilepticus in Richmond, Virginia. Epilepsia. 1999;40(6):752–8.View ArticlePubMedGoogle Scholar
  31. Husain AM, Horn GJ, Jacobson MP. Non-convulsive status epilepticus: usefulness of clinical features in selecting patients for urgent EEG. J Neurol Neurosurg Psychiatry. 2003;74(2):189–91.View ArticlePubMedPubMed CentralGoogle Scholar
  32. Leitinger M, Beniczky S, Rohracher A, Gardella E, Kalss G, Qerama E, Hofler J, Hess Lindberg-Larsen A, Kuchukhidze G, Dobesberger J, et al. Salzburg consensus criteria for non-convulsive status Epilepticus––approach to clinical application. Epilepsy Behav. 2015;49:158–63.View ArticlePubMedGoogle Scholar
  33. Dubey D, Alqallaf A, Hays R, Freeman M, Chen K, Ding K, Agostini M, Vernino S. Neurological autoantibody prevalence in epilepsy of unknown etiology. JAMA Neurol. 2017;74(4):397–402.View ArticlePubMedGoogle Scholar
  34. Vedeler CA, Antoine JC, Giometto B, Graus F, Grisold W, Hart IK, Honnorat J, Sillevis Smitt PA, Verschuuren JJ, Voltz R, et al. Management of paraneoplastic neurological syndromes: report of an EFNS Task Force. Eur J Neurol. 2006;13(7):682–90.View ArticlePubMedGoogle Scholar
  35. Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, Honnorat J, Smitt PS, Vedeler C, Verschuuren JJ, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004;75(8):1135–40.View ArticlePubMedPubMed CentralGoogle Scholar

Copyright

© The Author(s). 2018

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