Download Non-spinal radiculopathies

Spine problems that are actually
nerve problems
Shawn Jorgensen, MD
Albany Medical Center
AAPM&R Annual Assembly, October 2015
 None
 Radiculopathies

are a frequent problem
200-350/100,000 (Shelerud 2002)
 The
vast majority of radiculopathies are
spinal in origin
 What
about the patient without a clear
spinal cause on imaging and without an
unusual risk factor for rarer cause?
 What non-spinal causes are potentially hiding
in the typical patient in your waiting room?
 HIV



TB
Cryptococcus
Other fungi
 Syphilis
 Arachnoiditis
 Sarcoidosis
 GBS
 DM2
(Dumitru, 2002)
 What
about the patient without a clear
spinal cause on imaging and without an
unusual risk factor for rarer cause?


(1) Abnormal imaging, but mismatch
(2) Essentially normal imaging
 What
if imaging isn’t normal, but there is not
a good correlation between imaging and
clinical/EDX levels of pathology?

Suspicious pathology but one level off

Right C4-5 HNP with compression of exiting root
 Should be a right C5 radiculopathy
 Clinically



Numbness right lateral shoulder/arm
Weak deltoid, biceps
EDX

NEE abnormalities in deltoid, biceps, rhomboid major,
paraspinals
 What
if imaging isn’t normal, but there is not
a good correlation between imaging and
clinical/EDX levels of pathology?

Suspicious pathology but one level off

Right C4-5 HNP with compression of exiting root
 Should be a right C5 radiculopathy
 Clinically



Numbness right thumb, index finger
Weak wrist extension
EDX

NEE abnormalities in pronator teres, ECRL, paraspinals
 What
if imaging isn’t normal, but there is not
a good correlation between imaging and
clinical/EDX levels of pathology?

Suspicious pathology but one level off


Consider anomalous plexus anatomy
Plexus can be:
 Shifted (pre or postfixed)
 Expanded
 Contracted
 Altered in other ways
 Plexus

anomalies
Definitions



Normal plexus anatomy
 Large contribution from C5 and T1, occasional from
C4 or T2
Prefixed
 Large contribution from C4 with or without small
contribution from T1
Postfixed
 Large contribution from T2 with or without small
contribution from C5 (Pellerin 2010)
Post-fixed
Pre-fixed
Dorsal
Scapular
(C6)
(C4)
C4
C6
Suprascapular
(C6-7)
(C4-5)
C5
C7
C6
C8
C7
T1
C8
T2
Axillary
(C6-7)
(C4-5)
Ulnar
Ulnar
(C6-8)
(C8-T2)
 Plexus

anomalies
Frequency


Prefixed plexus
 10-63%, average around 33%
 More common than postfixed
 More common in women
Postfixed plexus
 0-72%, average around 15% (Pellerin 2010)
 Plexus

anomalies
Variation in posterior (sensory) roots



40/40 had at least one, 33/40 at least two
Most commonly between C6 and 7
Often process is thought to be one level higher than it
actually is (Perneczky 1980)
 What
if imaging is basically normal, without
any good anatomic (spinal) cause of the
radiculopathy?
 Consider non-spinal causes




Infectious
Inflammatory
Malignant
Motor neuron disease
 Infections




Major consideration in immunocompromised
In immunocompetent, otherwise healthy patients
they are not very common
Patients who have these infections rarely present
with isolated radicular symptoms
Red flags:

Fever, chills, night sweats, unexplained weight loss,
recent travel, history of infection (Shelerud 2002)
 Infections

Lyme disease






Multiorgan system disease caused by Borrelia
burgdorferi spirochete (bacteria)
Carried by the vector Ixodes scapularis or Ixodes
pacifica
Regionally specific: largely limited to northeastern and
nothern midwest USA
Typical symptoms include fatigue, fever, rash
(erythema migrans)
Neurological symptoms include peripheral (Bell’s palsy,
radiculopathy, mononeuropathy multiplex) and central
(meningitis, encephalitis)
Non-neurological symptoms include AV block and
arthritis
 Infections

Lyme radiculopathy



Will usually be in the setting of known disease with
other symptoms
6% of patients with Lyme disease (Brizzi 2014)
When to suspect (Logigian 1997):
 Exposure history
 Erythema migrans rash, other symptoms consistent
with Lyme disease
 No history of diabetes, no rash of shingles, no lab
evidence of diabetes, VZV, EBV, CMV
 Infectious

Lyme radiculopathy



Often polyradiculopathy (Watson 2002)
 Can be multifocal, involving an entire limb (Logigian
1997) or multiple limbs or regions (Logigian 1992)
Symptoms are often worse at night (Vallat 1987)
Thoracic radiculopathy about 25%, often involving
multiple dermatomes (Pachner 1985)
 Infectious

Lyme radiculopathy

Diagnosis
 “Erythema migrans (aka. Erythema chronicum
migrans or ECM) is the only manifestation of Lyme
disease in the United States that is sufficiently
distinctive to allow clinical diagnosis in the absence
of laboratory confirmation.” (Wormser 2007 IDSA
guidelines)
Erythema
migrans
rash
(bullseye)
 Infectious

Lyme radiculopathy

Diagnosis
 Labs

Early (Wormser 2007, IDSA guidelines)
 “Serological testing is too insensitive in the acute
phase, the first two weeks of infection, to be helpful
diagnostically. Patients should be treated on the basis
of clinical findings.”
 If equivocal, both acute and convalescent (2 weeks
after acute phase) serum samples should be tested
 Infectious

Lyme radiculopathy

Diagnosis
 Labs

Two-tiered approach (Wormser 2007, IDSA guidelines)
 ELISA
If negative, no Lyme disease
 If positive or equivocal, same sample retested by IgG and
IgM Western Blot/Immunoblot


Positive serology does not mean a given condition is due
to Lyme – reasonably high background seropositivity
rate (4%)
 Infectious

Lyme radiculopathy

Diagnosis
 CSF




Often with pleocytosis
Culture for B. burgdorferi
PCR for amplification of B. burgdorferi gene segments
80% have combination of positive lyme serology and
western blot, lymphocytic pleocytosis in CSF, and
CSF PCR or culture for B. burgdorferi (Logigian 1997)
 Infectious

Lyme radiculopathy

Treatment (Wormser 2007, IDSA guidelines)
 Early or late neurological disease



LP?
Ceftriaxone 2 grams daily for 14-28 days
Chronic neurological symptoms
 Response to treatment is slow and may be incomplete
 Retreatment not recommended unless relapse is
shown by reliable objective evidence
 “There is no convincing biological evidence for the
existence of symptomatic chronic B. burgdorferi
infection among patients after receipt of
recommended treatment regimens for Lyme disease”
(Wormser 2007, IDSA guidelines)
 Infectious

Varicella-Zoster virus (VZV)




Develop chickenpox as a child or are given vaccine
 Chickenpox <1 year of age increases risk of shingles
<60 years of age
Virus then becomes latent and resides in dorsal root
ganglia or cranial nerve ganglia for life
Reactivates with age (8-10x more common >60 years)
or immunosupression
Recurrence - <5% in immunocompetent (Gilden 2000)
 Infectious

Varicella-Zoster virus (VZV)


Most common in the cranial nerves and thoracic roots
(Gilden 2000)
Usually with a characteristic rash, but without –
Zoster sine herpete
 Infectious

Varicella-Zoster virus (VZV)

Zoster sine herpete
 Dermatomal distribution pain without rash
 True prevalence unknown
 Diagnosis




PCR of CSF or PMNs for amplification of VZV
(and not HSV)
Peripheral antibodies are of no value (all positive), but
antibodies in CSF are diagnostic (Gilden 2000)
Tends to recur (Gilden 1994)
Treatment

IV acyclovir, PO famciclovir (Gilden 2000)
 Infectious

Varicella-Zoster virus (VZV)


Usually only sensory complaints
Occasionally weakness – Zoster paresis
 Infectious

Varicella-Zoster virus (VZV)

Zoster paresis (Thomas 1972)
 Not clear if this is spread to anterior root or anterior
horn
 Anterior horn cells have no natural immunity
 Usually middle aged and elderly
 Timing



Always follows rash, from 1-5 weeks, usually within 2
weeks
All segments start simultaneously
Once paresis begins, culminates in hours-days
 Infectious

Varicella-Zoster virus (VZV)

Zoster paresis (Thomas 1972)
 Distribution





Right twice as common as left
Most often cervical and lumbosacral
Does not always coincide with sensory distribution – can
be widely separated
One or two segments most common, but can be
regional, involving entire limb
Outcome

>50% full recovery, 25% significant recovery
 Inflammatory

Sarcoidosis



Systemic autoimmune condition with predilection of
lymphatic, pulmonary, ocular systems
Characterized by lymphadenopathy, anergy,
hypercalcemia, uveitis, skin lesions, pulmonary
involvement
Neurosarcoidosis - ~5% of patients with sarcoid
(Delaney 1977)
 1% of thoracic radiculopathies in one series (Koffman
1998)
 22/23 neurological involvement was the
presenting/only complaint, usually CNS
 PNS involvement usually chronic (Delaney 1977)
 Inflammatory

Sarcoidosis

Diagnosis
 CSF





Pleocytosis
Elevated protein
Low glucose
Negative cytology and culture (Atkinson 1982)
Angiotensin converting enzyme (ACE) level
 Malignant



Can be from direct extension of primary tumor,
metastases, or paraneoplastic
Direct extension more common in plexopathies
(Watson 2002)
Radiculopathy usually from spinal or
leptomeningeal spread (Watson 2002)
 Malignant

Leptomeningeal metastases (Watson 2002)


Usually polyradicular
Usually not the sentinel sign of recurrence, but
diagnosed in the setting of known metastases
 Malignant

Leptomeningeal metastases (Watson 2002)

Diagnosis
 MRI

May show nodular, patchy enhancement or may be
negative
 Malignant

Leptomeningeal metastases (Watson 2002)

Diagnosis
 MRI


May show nodular, patchy enhancement or may be
negative
LP

May require 3 separate, high volume taps to show
cytology
 Malignant

Leptomeningeal metastases (Watson 2002)


Prognosis
 Poor
Treatment
 Palliative chemotherapy and intrathecal
methotrexate may prolong survival by months
 Motor


Pure motor with no sensory involvement
Often present as a radiculopathy


neuron disease
Anterior horn cell and pure motor root process –
indistinguishable
ALS, PMA and Hirayama disease are most likely to
present as a typical radiculopathy

Motor neuron disease

Hirayama disease (aka Juvenile segmental SMA,
Benign focal amyotrophy) (Amato 2008)


Epidemiology
 Usually between 15-25 years old
 Male>female
 Usually Asian descent
Clinical
 Progressive atrophy and weakness of hand and forearm
muscles for 6 years or less, then plateaus
 No sensory involvement
 No UMN signs
 1/3 involve other limb clinically, more subclinically
with EDX abnormal
 “Cold paresis” – weakness is worse in the cold
 Motor

neuron disease
ALS



Primarily motor process – no sensory involvement
UMN and LMN signs in same patient in most cases
Presents focally, often subacutely
 Polyradiculopathy




(McGonagle 1990)
5% of all studies in EMG lab
EDX findings cannot generally distinguish
between different causes
Most common cause is degenerative spine
processes, but several more ominous causes are
in the differential
Subsequent studies separated them into



Extradural
Intradural / extraaxial
Intraaxial

Polyradiculopathy (McGonagle 1990)

Extradural







Majority were degenerative spine conditions
Significantly older
More pain, less weakness
Slower progression
Less disability
CSF - increased protein was the only abnormality
Intradural/extraaxial





Younger
1/3 with bowel or bladder issues
Less pain
Progressed faster
CSF – usually established the diagnosis
 Summary

When to suspect a non-spinal radiculopathy




Imaging
 Normal imaging
 Abnormalities on imaging don’t match neurological
level clinically or on EDX
Neurological locations
 Polyradiculopathy
 Thoracic radiculopathy
Higher likelihood of systemic disease
 Background systemic disease (cancer, infection,
autoimmune disease, immunosupressed)
 Systemic signs (fever, weight loss)
Pure motor symptoms
 Summary

How to proceed when you encounter a likely nonspinal radiculopathy

Rational workup
 Imaging


MRI – everyone without contraindication
Contraindication – CT +/- myelogram

Summary

How to proceed when you encounter a likely nonspinal radiculopathy

Rational workup
 Signs of infection





Lyme titers (Western blot if positive)
PCR of PMNs for VZV
LP
 WBC, protein, glucose
 Culture Lyme, viral cultures
 PCR for Lyme, VZV, HSV
 Cytology (may need more than one)
ID consult
Pure motor

More widespread EDX testing looking for signs of motor
neuron disease

Bibliography
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
Atkinson BN, Ghelman B, Tsairis P, Warren RF, et al. Sarcoidosis presenting as cervical
radiculopathy. A case report and literature review. Spine 1982;7:412-416.
Brizzi KT, Lyons JL. Peripheral nervous system manifestations of infectious diseases.
Neurohospitalist 2014;4(4):230-240.
Burton JM, Kern RZ, Halliday W, et al. . Neurological manifestations of West Nile virus
infection. Can J Neurol Sci. 2003;31 (2):185–193 [PubMed]
Delaney P. Neurological manifestations of sarcoidosis. Ann Int Med 1997;87:336-345.
Gilden DH, Kleinshmidt-DeMasters BK, LaGuardia JJ, Mahalingam R, Cohrs RJ.
Neurological complications of the reactivation of varicella-zoster virus. N Engl J Med
2000;342(9):635-645.
Gilden DH, Wright RR, Schneck SA, Gwaltney JM Jr, et al. Zoster sine herpete, a
clinical variant. Ann Neurol 1994;35:350-353.
Halperin J. Lyme neuroborreliosis. Peripheral nervous system manifestations. Brain.
1990;113 (4):1207–1221 [PubMed]
Kleiner JB, Donaldson WF, Curd JG. Extraspinal causes of lumbosacral radiculopathy. J
Bone Joint Surg Am 1991;73A:817-821.
Koffman B, Junck L, Elias SB, Feit HW, Levine SR. Polyradiculopathy in sarcoidosis.
Muscle Nerve 1999;22:608-613.
Logigian EL. Peripheral nervous system Lyme borreliosis. Semin Neurol 1997;17(1):2530.
Logigian EL, Steere AC. Clinical and electrophysiologic findings in chronic neuropathy
of Lyme disease. Neurology 1992;42(2):303-311.

Bibliography
Majid A, Galetta SL, Sweeney CJ, Robinson C, Mahalingam R et al. Epstein-Barr virus
myeloradiculitis and encephalomyeloradiculitis. Brain 2002;125:159-165.
 Mayo DR, Booss J. Varicella zoster-associated neurologic disease without skin lesions.
Arch Neurol 1989;46:313-315.
 McGonagle TK, Levine SR, Donofrio PD, Albers JW. Spectrum of patients with EMG
features of polyradiculopathy without neuropathy. Muscle Nerve 1990;13:63-69.








Merchut MP, Gruener G. Segmental zoster paresis of limbs. Electromyo Clin Neurophys 1996;36:369375.
Pachner AR, Steere AC. The triad of neurological manifestations of Lyme disease:
Meningitis, cranial neuritis, and radiculoneuritis. Neurology 1985;35:47-53.
Pellerin M, Kimball Z, Tubbs RS, Nguyen S, et al. The prefixed and postfixed brachial
plexus: a review with surgical implications. Surg Radiol Anat 2010;32:251-260.
Perneczky A, Sunder-Plassmann M. Intradural variant of cervical nerve root fibers
potential cause of misinterpreting the segmental location of cervical disc prolapses
from clinical evidence. Acta Neurochir (Wien) 1980;52:79-83.
Ponka A, von Bonsdorff M, Farkkila M. Polyradiculitis associated with Mycoplamsa
pneumonia reversed by plasma exchange. Brit Med J 1983;286:475-476.
Scelsa SN, Hershkovitz S, Berger AR. A predominantly motor polyradiculopathy of Lyme
disease. Muscle Nerve 1996;19:780-783.
Schelerud RA, Paynter KS. Rarer causes of radiculopathy: spinal tumors, infections,
and other unusual causes. Phys Med Rehabil Clin N Am 2002;13:645-696.

Bibliography








Sejvar JJ, Haddad MB, Tierney BC, et al. Neurologic manifestations and outcome of West Nile
virus infection. JAMA 2003;290(4):511-515.
Sharma KR, Sriram S, Fries T, Bevan HJ, Bradley WG. Lumbosacral radiculoplexopathy as a
manifestation of Epstein-Barr virus infection. Neurology 1993;43:2550-2554.
Silbert PL, Radhakrishnan K, Litchy WJ. The spectrum of thoracic radiculopathy: what is an
appropriate evaluation? Neurology 1995;55 (Suppl 2):A307.
Thomas JE, Howard FM. Segmental zoster paresis – a disease profile. Neurology 1972;22:459466.
Vallat JM, Hugon J, Lubeau M, et al. Tick-bite meninogradiculoneuritis: Clinical,
electrophysiological, and histological findings in 10 cases. Neurology 1987;37:749-753.
Van Alfen N, van Engelen BG. The clinical spectrum of neuralgic amyotrophy in 246 cases.
Brain 2006;129:438-450.
Vanneste JA, Bronner IM, Laman DM, et al. Distal neuralgic amyotrophy. J Neurol
1999;246:399-402.
Watson J. Office evaluation of spine and limb pain: spondylotic radiculopathy and other
nonstructural mimickers. Semin Neurol 2011;31:85-101.

Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, et al. The Clinical Assessment, Treatment, and
Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice
Guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases 2007;45:10891134.

Younger DS, Rosoklija G, Hays AP. Persistent painful Lyme radiculoneuritis. MuscleNerve
995;18:359-360.