Download A Diagnosis Challenge-L4 Nerve Root Compression as the Initial

CASE REPORTS
A Diagnosis Challenge-L4 Nerve Root Compression as the Initial Presentation
of Chronic Inflammatory Demyelinating Polyneuropathy
INIMIOARA MIHAELA COJOCARU1,3, MARILENA ALEXIANU2, ALEXANDRA BASTIAN2,
VIOLETA SAPIRA3, CRISTINA HERŢEA3, M. COJOCARU4
1
“Carol Davila” University of Medicine and Pharmacy, 3Department of Neurology,
“Colentina” Clinical Hospital, Bucharest, Romania
2
Department of Neuropathology, “Colentina” Clinical Hospital, Bucharest, Romania
4
“Titu Maiorescu” University, Faculty of Medicine, Department of Physiology, Bucharest, Romania
The authors present the case of a 65-year-old woman who was admitted for paraparesis and
paresthesias in the inferior limbs. The neurological examination revealed the difficulty in extension of
the right foot and of the right toe, accompanied by paresthesias located in the anterolateral area of the
right leg, dorsum and plantar area of the foot, the reduction of the right knee jerk, and of the ankle
tendon jerk both sides. The vertebro-spinal MRI showed lumbar canal stenosis with L4 intraforaminal
compression on the right, and L2-L3 on the left. CSF examination revealed mild increase in protein
concentration. The morphological picture of the sural nerve biopsy was compatible with a chronic
inflammatory neuropathy and severe muscular lesions of neurogenic origin were observed on right
gastrocnemius muscle biopsy. The diagnosis of chronic inflammatory demyelinating polyneuropathy
(CIDP) was established. Solu-medrol (0.5 g/d)-5 days, then medrol (prednisolone) was done, followed by
improving of the symptomatology. For the relapse of the disease intravenous immunoglobulins
(IVIG)-0.4 g/kg/d-5 days was the elective treatment. Six months later she presented a new relapse.
IVIG were administered with the remission of the sensitive symptoms. A chronic treatment with
medrol was recommended. The diagnosis of L4 disc herniation was obvious in the studied case, but
the electroneurographic examination brought extra data for the associated diagnosis of CIDP whose
onset was asymmetrical and initially paucisymptomatic. Neither the electroneurographic examination
nor the CSF examination were total relevant for CIDP, imposing the sural nerve biopsy. The diagnosis
of CIDP involves a team-work composed of neurologist, electroneurophysiologist and neuropathologist.
Key words: chronic inflammatory demyelinating polyneuropathy (CIDP), electroneurographic
and electromyographic examination, nerve and muscle biopsy.
Chronic inflammatory demyelinating polyneuropathy (CIDP), a form of polyneuropathy,
separated from acute inflammatory polyradiculopathy or Guillain-Barré syndrome by Austin in
1958, on the basis of duration of evolution,
neuropathological aspect and responsiveness to
corticosteroids, raises diagnosis problems.
The prevalence of CIDP is estimated to range
from 1.0–7.7 cases per 100,000 people, a likely
underestimate related to differing diagnosis criteria
and underreporting.
CASE PRESENTATION
We present the case of a 65-year-old woman,
with a history of essential hypertension and renal
lithiasis, who was admitted at the end of December
2010 in the Neurologic Department of “Colentina”
Clinical Hospital for paraparesis and paresthesias
in the inferior limbs.
ROM. J. INTERN. MED., 2012, 50, 4, 297–308
The clinical presentation started two months
ago with difficulty in extension of the right foot
and of the right toe, accompanied by paresthesias
located in the anterolateral area of the right leg,
dorsum and plantar area of the foot, without
improvement after symptomatic therapy.
The patient was hospitalized at the beginning
of December 2010 in the Neurosurgery Department
of “Bagdazar-Arseni” Emergency Clinical Hospital.
The motor deficit was evaluated according to
ASIA classification as follows: L4-no points, L5-2
points, S1–4 points, reaching a total of 16 of 25 on
the right side. On the left side the total was of 24
out of 25 left and right, summarising a total score
of 90 out of 100 points.
The neurological examination also revealed
the reduction of the right knee jerk, and of the
ankle tendon jerk both sides.
The vertebro-spinal MRI showed lumbar
canal stenosis with major injury of the L2, L3, L4
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discal plans with L4 intraforaminal compression on
the right, and L2-L3 on the left, left ureterohydronephrosis.
The cardiologic examination found essential
hypertension.
The abdominal ultrasound investigation demonstrated left pielocaliceal dilatation.
The case was suited for neurosurgical
intervention, but that could not be done without
further ancillary tests.
The electroneurographic tests showed bilateral
decrease in sensitive conduction velocities of the
superficial peroneus, but especially on the right
side and bilateral decrease of motor conduction
velocities of the common peroneus and posterior
tibial. Raised motor distal latencies were also
recorded in the tibial nerves.
Both decreased amplitudes of CMAP and
present F waves with raised latencies were recorded
in the tibial nerve on both sides. A waves were
present on the right side.
The electromyographic study observed chronic
neurogenic highly active recording of the anterior
tibial muscles, especially on the right, and stable
chronic neurogenic recording of the gastrocnemian
muscles, and of the first interosseous digiti.
The ancillary tests raised the question: is it
CIDP or a mixed form in evolution?
At the admission in the Neurologic Department
of “Colentina” Clinical Hospital the patient’s
general and neurological examination provided no
further data.
The laboratory tests showed an inflammatory
syndrome and dyslipidemia, but they were non
relevant for collagen disease, vasculitis, thyroid
disorder, neoplasias, immunoglobulin M monoclonal
gammopathy with anti myelin associated glycolprotein antibody (anti-MAG), hepatitis viruses
infection, cryoglobulinemia, Borrelia burgdorferi
infection, sarcoidosis, syphilis or HIV infection.
CSF examination revealed a clear macroscopic aspect with normal values of elements
(4 elements/mm3), glucose concentration (68 mg/dL),
chloride concentration (139 mEq/L), and mild
increase in protein concentration (0.76 g/L) (normal
values 0.2–0.3 g/L).
A right sural nerve and right gastrocnemius
muscle biopsy was done.
Right sural nerve biopsy: the sensitive nerve
fragment obtained by biopsy showed mixed axonal
degeneration and segmental demyelination lesions.
2
The axonal degeneration lesions seemed to be the
primary ones: 7% of the teased myelinic fibers had
myelinic ovoids and bullae, the second peak of the
myelinic fiber histogram was practically absent, the
histogram was shortened, and the myelinic fiber
density was mildly decreased (6.167 fb/mm2) (N =
7,000–11,000 fb/mm2). Segmental demyelination
lesions on 4% of the teased myelinic fibers were
associated (Fig. 1). No inflammatory lesions were
observed on the examined fragment (Photo 1).
Conclusion: the morphological picture of the
biopsied nerve fragment was compatible with a
chronic inflammatory neuropathy.
Right gastrocnemius muscle biopsy: muscular
fragment presenting a nearly normal architecture
and a moderate fiber size variability. On this
background small and large groups of fibers in
severe/extreme atrophy and nuclear clumps could
be observed. Atrophic fibers had frequently an
elongated contour, the very severely atrophic ones
were rounded. One necrotic fibre. Generally the
muscle fiber internal structure was normal, but in
some areas targetoid fibres could be observed. The
number of type II muscular fibres was severely
reduced, but in some fascicles type II muscle fibers
formed groups up to 35 fibers realizing the type
grouping aspect. Both histoenzymatic muscle fiber
types were affected by atrophy (Photo 2–10).
Conclusion: severe muscular lesions of
neurogenic origin.
Considering all the ancillary tests, the final
diagnosis were:
– Chronic inflammatory demyelinating polyneuropathy (CIDP)
– L2–L3 and L4 lumbar canal stenosis
– Essential hypertension stage III high
additional risk group
– Mixed dyslipidemia
Solumedrol (0.5 g/d)-5 days, then medrol
(prednisolone)-32 mg/d, analgesics, hypotensors,
hypolipemiants, gastroprotectors were administered
and kinetotherapy was done.
The clinical course was favorable, the algic
and paresthesic symptoms in the right inferior limb
improved.
At discharge, the treatment recommended
was with medrol-32 mg/d, gabaran-600 mg/d,
thiogamma (benfothiamine)-1200 mg/d, hypotensors,
diuretics, hypolipemiants, low fat diet, low glucose
diet, no salt, kinetotherapy, and the monitoring of
glycemia and kaliemia.
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A Diagnosis Challenge-L4 Nerve Root Compression
In June 2011 the patient is readmitted for
worsening of the right limb motor deficit due to
anterior tibial nerve palsy. Intravenous immunoglobulins (IVIG)-0.4 g/kg/d-5 days was the elective
treatment and oral antidiabetics were added.
The clinical picture completed in December
with dysesthesias and burning sensation at the
distal level of the inferior limbs. IVIG were
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administered for 5 days with the remission of the
sensitive symptoms.
A chronic treatment with medrol with
glycemic and kaliemic monitoring was recommended, and the patient did not present a relapse of
the disease until now.
A new neurosurgical examination was
indicated in order to assess the disc herniation.
histogram
HistogramaMyelinic
axonifiber
mielinici
5375
Teasing
Myelinic fiber no. %
nr.fibre
m ielinice %
40
N = 78%
R = 11 %
DS= 4 %
DA= 7%
35
30
25
20
15
10
5
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Diameter (microns)
Diametru (microni)
Fig. 1 Myelinic fiber histogram.
Photo 1. Cryosection in sural nerve. Gömöri, ob. 20.
Photo 2. Semithin section in the sural nerve. Toluidine blue, ob. 100.
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Photo 3. Small group of atrophic fibers and an isolated,
elongated atrophic fiber. HE, ob. 20.
Photo 4. Small group of atrophic fibers. HE, ob. 49.
Photo 5. Larger group of atrophic fibers. HE, ob. 20.
Photo 6. Small group of atrophic fibers. Gömöri, ob. 40.
Photo 7. Targetoide fibres. DPNH, ob. 10.
Photo 8. Small number of type II fibers. ATP-9.4, ob. 40.
Photo 9. Extreme reduction of type II fiber number.
ATP-9.4, ob. 10.
Photo 10. Type grouping of muscle fibers.
ATP-9.4 ob. 10.
4
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A Diagnosis Challenge-L4 Nerve Root Compression
DISCUSSION
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated
neuropathy characterized by a relapsing or a
progressive course.
The diagnostic approach involves appropriate
clinical examination, supportive laboratory and
electroneurophysiologic abnormalities, and in some
cases nerve biopsy [1].
By definition, symptoms and signs of a
neuropathy must be progressive for at least
2 months, which distinguishes CIDP from GuillainBarré syndrome (GBS) or the most common form
of GBS, namely acute acquired inflammatory
demyelinating neuropathy (AIDP) [2–4].
Some authors describe four courses of
progression in patients with CIDP: 1) chronic
monophasic (15%); 2) chronic relapsing (fluctuations
of muscular weakness or improvement over weeks
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or months) (34%); 3) stepwise progressive (34%);
4) steady progressive (15%).
CIDP presents a peak incidence at about 40–
60 years, but it can manifest in children [2][4]. The
relapsing form often presents in the twenties [2].
There is a slight increase prevalence in men.
Pregnancy can be associated with relapses or
exacerbations of the neuropathy [5]. Infections may
precede 20–30% of CIDP relapses or exacerbations
[6][7].
Most patients manifest with progressive,
symmetric proximal, and distal weakness.
American Academy Of Neurology Research
Criteria For Diagnosis Of Chronic Inflammatory
Demyelinating Polyneuropathy (CIDP) are presented
in Table I.
Supportive criteria for CIDP are summmarized
in Table II.
Diagnostic categories of CIDP are presented
in Table III.
Table I
American Academy of Neurology Research Criteria for Diagnosis
of Chronic Inflammatory Demyelinating Polyneuroppathy (CIDP)
I. Clinical
A. Mandatory
1 Progressive or relapsing motor and sensory, rarely only motor or sensory, dysfunction of more than one limb of peripheral
nerve nature, developing over at least 2 months
2 Hypo-or areflexia. This will usually involve all four limbs
B.
Supportive
1 Large fiber sensory loss predominates over small-fiber sensory loss
2 Exclusion
3 Mutilation of hands or feet, retinitis pigmentosa, ichthyosis, history of drug or toxic exposure known to cause a similar
peripheral neuropathy, or family history of a genetically based peripheral neuropathy
4 Sensory level
5 Unequivocal sphincter disturbances
II. Physiologic studies
A. Mandatory
Nerve conduction studies including studies of proximal nerve segments in which predominant process is demyelination
Must have three of four:
1. Reduction in conduction velocity (CV) in two or more motor nerves
a. <80% of lower limit of normal (LLN) if amplitude >80% of LLN
b. <70% of LLN if amplitude >80% of LLN
2. Partial conduction block or abnormal temporal dispersion in one or more motor nerves: peroneal nerve between ankle and
below fibular head, median nerve between wrist and elbow, or ulnar nerve between wrist and below elbow
Criteria suggestive of partial conduction block: <15% change in duration between proximal and distal sites and >20% drop
in negative-peak (-p) area or peak-to-peak (p-p) amplitude between proximal and distal sites Criteria for abnormal
temporal dispersion and possible conduction block:
>15% change in duration between proximal and distal sites and >20% drop in -p area or p-p amplitude between proximal
and distal sites. This criteria are only suggestive of partial conduction block, as these are derived from studies of normal
individuals. Additional studies, such as stimulation across short segments or recordings of individual motor unit potential,
are required for confirmation.
3. Prolonged distal latencies in two or more nerves
a. >125% of upper limit of normal (ULN) if amplitude >80% LLN
b. >150% of ULN if amplitude <80% of LLN
4. Absent F waves or prolonged minimum F-waves latencies (10–15 trials) in two or more nerves
a. >120% of ULN if amplitude >80% of LLN
b. >150% of ULN if amplitude <80% of LLN
B
Supportive
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1. Reduction in sensory VC < 80% of LLN
2. Absent H reflexes
III. Pathologic features
A. Mandatory
1. Nerve biopsy showing unequivocal evidence of demyelination and remyelination
2. Demyelination by either electron microscopy (>5 fibers), or teased fibers studies (>12% of 50 teased fibers, minimum of
four internodes each, demonstrating demyelinisation/remyelinisation)
B.
Supportive
1. Subperineural or endoneural edema
2. Mononuclear cell infiltration
3. “Onion-bulb” formation
4. Prominent variation in the degree of demyelinisation between fascicles
C.
Exclusion
1. Vasculitis, neurofilamentous swollen axons, amyloid deposits, or intra-cytoplasmic inclusions in Schwann cells or
macrophages, indicating adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy, or other
evidence of specific pathology
IV. CSF studies
A. Mandatory
1. Cell count <10/mm3 if HIV seronegative or >50/mm3 if HIV seropositive
2. Negative VDRL
B.
Supportive
1. Elevated protein
[3]
Table II
Supportive criteria for CIDP
A. Elevated cerebrospinal fluid protein with leukocyte count <10/mm3 (Recommendation Level A)
B. Magnetic Resonance Imaging showing gadolinium enhancement and/or hypertrophy of the cauda equina, lumbosacral or cervical
nerve roots, or the brachial or lumbosacral plexuses (Recommendation Level C)
C. Nerve biopsy showing unequivocal evidence of demyelination and/or of remyelination in >5 or more fibres by electron
microscopy or in >6 of 50 teased fibres
D. Clinical improvement following immunomodulatory treatment (Recommendation Level A)
Table III
Diagnostic categories of CIDP
Definite CIDP
Clinical criteria IA or B and II with electrodiagnostic criteria I; or
Probable CIDP + at least one supportive criterion; or
Possible CIDP + at least two supportive criteria
Probable CIDP
Clinical criteria IA or B and II with electrodiagnostic criteria II; or
Possible CIDP + at least one supportive criterion
Possible CIDP
Clinical criteria IA or B and II with electrodiagnostic criteria III
CIDP (definite, probable, possible) associated with concomitant diseases
[3] [8–11]
If weakness remains distal, other diagnoses
need to be considered (e.g. hereditary demyelinating neuropathy and paraprotein-related DADS
neuropathy). Although most patients (at least 80%)
have both motor and sensory involvement, a few
patients may have pure motor (10%) or pure
sensory (5–10%) symptoms and signs [2][12][13].
Subjective numbness in the extremities is
present in 68–80% of patients, while painful
paresthesias occur in 15–50% of patients [4][12].
Sensory examination is abnormal in most
patients, particularly large-fibers modalities (vibration
and touch) [2][4][12].
Some patients present sensory ataxia and gait
imbalance. Most patients with CIDP are areflexic
or at least hyporeflexic. Symptomatic autonomic
neuropathy (e.g. orthostatic hypotension, incontinence,
and impotence) can occur but it is uncommon
[4][14][15].
Rarely, some patients may present only
sensory signs and symptoms, a so-called “chronic
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A Diagnosis Challenge-L4 Nerve Root Compression
sensory demyelinating neuropathy” [16][17]. CIDP
may present sensory symptoms at the onset, and
motor symptoms later.
Cranial neuropathies may cause mild facial
weakness, ophthalmoparesis, dysarthria, dysphagia,
deafness or vertigo. A rare symptom at the onset is
neck extension weakness leading to dropped head
syndrome [18].
Papilledema may be observed in a few
patients, particularly in those with a CIDP-line
neuropathy related to POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes). Respiratory
insuficiency secondary to intercostal muscles and
diaphragm is rare in idiopathic CIDP, and
development should also make one consider POEMS
[4][19]. As POEMS is frequenly associated with an
303
osteosclerotic myeloma, a skeletal survey and scans
for focal plasmocytomas or lymphoma should be
performed.
As many as 3% of patients with CIDP
develop evidence of CNS demyelination of CNS
clinically, electrophysiologically (evoked potential
studies) or by MRI scans [20][21]. Attacks of CNS
demyelination can precede or follow the onset of
CIDP or may be entirely asymptomatic lesions. It
is unclear if these patients have multiple sclerosis
or a distinct immunologic disorder of the CNS.
Several medical conditions, especially other
autoimmune disorders, HIV infection, and immunoproliferative disorders/malignancies are associated
with CIDP or a CIDP-like neuropathy (Table IV)
[2][3][22][23–29].
Table IV
CIDP in association with concomitant diseases
One of the following is present:
a.
Conditions in which, in some cases, the pathogenesis and pathology are thought to be the same as in CIDP
Diabetes mellitus
HIV infection
Chronic active hepatitis
IgA or IgG monoclonal gammopathy with undetermined significance
IgM monoclonal gammopathy without antibodies to myelin associated glycoprotein (MAG)
Systemic lupus erythematosus or other connective tissue disease
Sarcoidosis
Thyroid disease
Inflammatory bowel disease
b. Conditions in which the pathogenesis and pathology may be different from CIDP
Borrelia burgdorferi infection (Lyme disease)
Paraneoplastic
POEMS syndrome
Lymphoma
Castelman disease
IgM monoclonal gammopathy of undetermined significance with antibodies to myelin
associated glycoprotein (MAG)
Waldenström’s macroglobulinemia (usually associated with DADS phenotype)
Small cell carcinoma of the lung
Carcinoma of the pancreas
Carcinoma of the colon
Cholangiocarcinoma
Melanoma
Osteosclerotic myeloma
Others (vasculitis)
Bone marrow and solid organ transplantations (often in setting of graft-vs.-host disease or rejection)
Neurotoxicity
Rarely, patients with diabetes mellitus develop
a CIDP-like neuropathy with symetric proximal and
distal extremity weakness, elevated CNS protein,
and demyelinating features on the nerve conduction
study (NCS) and nerve biopsies [30–34]. These
patients may have an unusual form of diabetic neuropathy, incidental occurrence of CIDP, or a predisposition toward developing CIDP due to their diabetes.
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Inimioara Mihaela Cojocaru et al.
A toxic-induced neuropathy, resembling to
CIDP, has been assoociated with certain medications
such as cyclosporine, tacrolimus and TNF-alpha
blockers [22][35][36]. It is likely that CIDPs in those
cases are not caused by a direct toxic effect; rather,
these medications alter the immune status of treated
individuals and may predispose them to CIDP.
Pathology
Nerve biopsies may reveal segmental demyelination and remyelination but due to multifocal
process these are not always evident [2][4][37][38].
Chronic demyelination and remyelination
result in proliferation of Schwann cell processes
forming the so-called “onion bulbs”.
Schwann cell proliferation can lead to a
hypertrophic appearance of the nerve. The number
of myelinated fibers is usually reduced. Teased
nerve fibers analysis demonstrated segmental
demyelination and/or remyelination in 23–46%,
axonal degeneration in 21–42%, mixed demyelinating and axonal features in 12.5% and normal
findings in 18–43.5% of teased nerve fibers [2][4].
Endoneurial and perineurial edema may also
be appreciated on biopsy. Inflammatory cell infiltrate
may be evident in the epineurium, perineurium, or
endoneurium, and it was usually perivascular, but it
is often quite subtle or absent on sural nerve
biopsies [31][40].
Inflammatory cells are better appreciated
with immunostaining for lymphocytes [31] [40].
The inflammatory component comprises of macrophages, CD3 ± activated T cells (mainly CD8+ but
CD4+ cells lymphocytes) and dendritic cells [40].
Of note, a similar frequency of inflammatory cell
infiltrate within nerves is seen in a variety of
neuropathies, raising concern regarding the pathogenic role of these cells [39]. The matrix metalloproteinases MMP-2 and MMP-9 (gelatinases A and B)
are overexpressed in the peripheral nerves in
patients with CIDP [41]. These enzymes that are
secreted by T cells are capable of digesting basement
membrane proteins, thereby facilitating the infiltration of inflammatory cells into peripheral nerves.
Nerve biopsy is not essential for the diagnosis
of CIDP, but it remains a useful diagnostic tool
[38][42], especially when lymphomatous infiltration,
amyloidosis, or sarcoidosis may mimic CIDP.
On electronmicroscopy, macrophages may be
appreciated penetrating the basement membrane and
displacing of Schwann cell cytoplasm, lysing the
superficial myelin lamellae, penetrating along
8
intraperiod lines, and engulfing the dysrupted
myelin by endocytosis. Subsequently, Schwann
cells are recruited to remyelinate the demyelinated
internodes. The demyelinated axons diminish in
diameter as much as 50%, but later regain some of
their diameter following remyelinisation. The proliferation of Schwann cell processes and basement
membrane following relapses of demyelination and
remyelination can lead to onion-bulb formations
seen on biopsy.
Pathogenesis
The immunopathogenesis of CIDP shows that
autoreactive T-cells recognize a specific autoantigen in the context of major histocompatibility
complex class II and costimulatory molecules on
the surface of antigen-presenting cells (macrophages) in the systemic immune compartment.
An infection may trigger this event through
molecular mimicry, a cross-reaction toward epitopes
shared between microbial agent and nerve antigens.
These activated T lymphocytes can cross the bloodnerve barrier in a process involving cellular
adhesion molecules, matrix metalloproteinases, and
chemokines.
Within the peripheral nervous system, T cells
activate macrophages, that enhance phagocytic
activity, the production of cytokines, and the
release of toxic mediators, including nitric oxide,
reactive oxygen species, matrix metalloproteinases,
and proinflammatory cytokines including tumor
necrosis factor (alpha) and interferon (gamma).
Autoantibodies crossing the blood-nerve
barrier or locally produced by plasma cells contribuite
to demyelination and axonal damage. Autoantibodies may mediate demyelination by antibodydependent cellular cytotoxicity, potentially block
epitopes that are functionally relevant for nerve
conduction, and activate the complement system by
the classic pathway, yielding proinflammatory
mediators and the lythic membrane-atack complex
C5b-9. Termination of the inflammatory response
occurs through the induction of T-cell apoptosis
and the release of anti inflammatory cytokines,
including interleukin-10 and transforming growth
factor (beta).
The myelin sheath (inset) is composed of
various proteins, such as myelin protein zero,
which account for more than 50% of the total
membrane protein in human peripheral nervous
system myelin, myelin protein 2, myelin basic
protein, myelin-associated glycoprotein, connexin
32, and gangliosides and related glycolipids.
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A Diagnosis Challenge-L4 Nerve Root Compression
These molecules have been identified as
target antigens for antibodies responses with varying
frequencies in patients with this disease [1].
Treatment
Corticosteroids
The administration of prednisone was superior
to no treatment [43] (Class II evidence). Six weeks
of oral prednisolone starting at 60 mg daily
produced benefit that was not significantly different
from that produced by a single course of IVIG 2.0 g/kg
[44][45] (Class II evidence). There are many
observational studies reporting a beneficial effect
from corticosteroids except in pure motor CIDP in
which they have sometimes appeared to have a
harmful effect [46]. Consequently, a trial of
corticosteroids should be considered in all patients
with significant disability (Recommendation Level
B). There is no evidence and no consensus about
whether to use daily or alternate day prednisone or
prednisolone or intermittent high dose monthly
intravenous or oral regimen [47].
Plasma exchange (PE)
Plasma exchange provides significant shortteme benefit in about two-thirds of patients, but
rapid deterioration may occur afterwards [48][49].
PE might be considered as an initial treatment
(Recommendation Level A). However, because
adverse events related to difficulty to venous
access, use of cytrate and haemodynamic changes
are not uncommon, either corticosteroids or IVIG
should be considered first (Good Practice Point).
Intravenous imunoglobulin (IVIG)
Intravenous imunoglobulin 2.0 g/kg produces
significant improvement of disability lasting 2–6
weeks [50][51][45] (Class I evidence). As the
benefit from IVIG is short lived, treatment, which
is expensive, needs to be repeated at intervals that
need to be judged on an individual basis. Crossover
trials have shown no significant short-term
difference between IVIG and PE [52] or between
IVIg and prednisolone [44], but the samples were
too small to establish equivalence (both Class II
evidence).
Immunosuppressive agents
Azathioprine showed no benefit when added
to prednisone [53]. Immunosuppressive agents are
often used together with corticosteroids to reduce
the need for IVIG or PE or to treat patients who
have not responded to any of these treatments but
there is only class IV evidence on which to base
this practice [53]. The immunosuppressant
305
treatment may be considered when the response to
corticosteroids, IVIG or PE, is inadequate (Good
Practice Point).
Interferons
Intramuscular administration of beta interferon 1a 30 mcg weekly improved clinically 7 out
of 20 patients [54][55]. Interferon alpha administration improved 9 out of 14 treatment-resistant
patients [56]. Interferon treatment may be considered
when the response to corticosteroids, IVIG or PE,
is inadequate (Good Practice Point).
Other therapeutic options are cyclosporin,
methotrexate, cyclophosphamide, mycophenolate
mofetil, total lymphoid irradiation [57].
Initial management (Good Practice Point)
Patients with very mild symptoms that do not
or very slightly interfere with activities of daily
living may be monitored without treatment. Urgent
treatment with corticosteroids or IVIG should be
considered for patients with moderate or severe
disability. Common initial dozes of corticosteroids
prednisolone or prednisone 1 mg/kg or 60 mg/daily
but there is a wide variation in practice [47]. The
usual first dose of IVIG is 2.0 g/kg given as 0.4 g/kg
on five consecutive days. Contraindications to
corticosteroids will influence the choice towards
IVIG and vice versa. For pure motor CIDP IVIG
treatment should be the first choice and if
corticosteroids are used, patients should be monitored
closely for deterioration.
Long-term management (Good Practice Point)
No evidence-based guideline can be given as
any of the trials systematically assessed long-term
management, each patient requires assessment on a
individual basis. For patients starting on corticoids
a course up to 12 weeks on their starting dose
should be considered before deciding whether there
is no treatment response. If there is a response,
tapering the dose to a low maintenance level one or
two years and possibly withdrawal should be
considered. For patient starting on IVIG, observation
to discover the occurrence and duration of any
response to the first course should be considered
before embarking on further treatment. If patients
respond to IVIG, and then worsen, further and
ultimately repeated doses should be considered.
Repeated doses may be given over one or two days.
The amount per course needs to be titrated
according to the individual response. Repeat
courses may be needed every 2–6 weeks. If
frequent high dose IVIG is needed, the addition of
corticosteroids or of an immunosuppressive agent
should be considered. Approximately 15% of
patients fail to respond to any of these treatments
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Inimioara Mihaela Cojocaru et al.
because of severe secondary axonal degeneration
that takes years to improve.
CONCLUSION
1) The diagnosis of L4 disc herniation was
obvious in the studied case, but the electroneurographic examination brought extra data for
10
the associated diagnosis of CIDP whose onset was
asymmetrical and initially paucisymptomatic.
2) Neither the electroneurographic examination
nor the CSF examination were totally relevant for
CIDP, imposing the sural nerve biopsy.
3) The diagnosis of CIDP involves a team
work composed of a neurologist, an electrophysiologist and a neuropathologist.
Autorii prezintă cazul unei paciente de 65 ani care s-a internat pentru
parapareză şi parestezii la nivelul membrelor inferioare. Examinarea neurologică
a relevat extensie dificilă a piciorului drept şi a halucelui drept, asociată cu
parestezii la nivelul regiunii anterolaterale a gambei drepte, feţei dorsale şi
plantare a piciorului, diminuarea reflexului rotulian drept şi a reflexului achilian
bilateral. Examenul MRI vertebro-medular a evidenţiat stenoză a canalului lombar
cu compresie intraforaminală L4 de partea dreaptă şi L2-L3 de partea stângă.
Examinarea LCR a relevat hiperproteinorahie moderată. Aspectul anatomopatologic
al biopsiei nervului sural a fost de neuropatie inflamatorie cronică şi cel al
biopsiei muşchiului gastrocnemian drept de leziuni musculare severe secundar
neurogene. S-a stabilit diagnosticul de polineuropatie inflamatorie demielinizantă
cronică (CIDP). S-a administrat solu-medrol (0,5 g/zi)-5 zile, apoi medrol
(prednisolon), urmat de ameliorarea simptomatologiei. La un nou puseu al bolii
s-au administrat imunoglobuline iv-0,4 g/kgc/zi-5 zile ca tratament de elecţie.
După şase luni pacienta a prezentat un nou puseu, s-au administrat IGIV cu
remisiunea simptomelor senzitive. S-a recomandat tratament cronic cu medrol.
Diagnosticul de hernie de disc L4 a fost evident la cazul studiat, dar examenul
electroneurografic a adus date suplimentare pentru diagnosticul asociat de CIDP
al cărei debut a fost asimetric şi initial paucisimptomatic. Nici examenul
electroneurografic, nici cel al LCR nu au fost relevante în totalitate pentru CIDP,
impunând biopsia nervului sural. Diagnosticul de CIDP implică munca în echipă
formată din neurolog, electroneurofiziolog şi anatomopatolog.
Corresponding author: Inimioara Mihaela Cojocaru, MD, PhD, Senior lecturer
“Colentina” Clinical Hospital, Department of Neurology
19–21 Şos. Ştefan cel Mare, 020125, Bucharest, Romania
E-mail: [email protected]
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Received October 20, 2012