|A 33 year old man was admitted to the Emergency Department
(ED) in the summer of 2014 with complaints of fever (up to 38-
38.5°C), dysuria and urine retention. An urethral catether was
placed with resolution of the retention and the patient was
referred to an urological unit. The diagnosis of prostatitis was
established and it was started an antibiotic course. Three days
later, the patient reported unstable gait, numbness and weakness
in the distal parts of the upper and lower limbs. The weakness
in the extremities had an ascendent, progressive course, as
the condition progressed to quadriparesis in just 24 hours. The
patients was admitted to the Department of Neurology because
of the neurological nature of the symptoms.
|The primary neurological examination showed:
|• Moderate to severe central paraparesis of the lower limbs
and latent central paresis of the upper limbs
|• Th3 – th4 sensory level
|• Pelvic reservoir dysfunction, manifested as urine retention
|• Three days later additional neurological symptoms appeared – bilateral peripheral lesions of nn. Faciales, more pronounced
in the left, lesion of the left n. Abducens
|• Transient dysphagia and dysartria.
|The laboratory studies revealed increased non-specific
inflammatory markers (erythrocyte sedimation rate – ESR,
C-reactive protein, fibrinogen), thrombocytopenia (90 – 114 x
109/l), borderline serum creatinine (138 – 147 mkmol/l). A lumbal
punction was performed and the cerebrospinal fluid (CSF) was
examined. It showed increased total protein 1.55 g/l (reference
level 0.15-0.45 g/l), normal cell count, normal glucose level.
The CSF electrophoresis was notable for high γ-fraction without
mono- or oligoclonal bands. The microbiological studies of the
former were negative for enterovirus, West Nile virus, Tickborne
encephalitis, Human immunodeficiency virus 1, 2 (HIV-
1; HIV-2), Herpex simplex virus 1 and 2, Varicella zoster virus.
Cytomegalovirus. Nasal, throat, urine and hemocultures were
|A magnetic-resonance tomography (MRT) of the cervicothoracic
spine showed altered signal along the T1-T4 segment. At the same
level, edema in the white and gray matter of the myelon was
noted (Figure 1). After contrast application, a disruption of the
blood-brain barrier was observed at level C5-T4. A MRT of the head was also performed, showing altered signal in the thalamus
and left middle cerebellar peduncule – changes associated with
increased fluid content (Figure 2). There was no blood-brain
barrier disruption after contrast administration.
|The changes in the spinal cord and the brain were interpretated
as inflammatory demyelinating condition – acute disseminated
encephalomyelitis/transversal myelitis – active phase.
|The electroneuromyography (ENMG) study demonstrated
polyneuropathy – demyelinating type with secondary axonal
damage of the sensory and motor nerves. The findings were
consistent with acute inflammatory polyneuropathy.
|The differential diagnosis included the following:
|1. Acute inflammatory demyelinating polyradiculoneuropathy,
Guillaine-Barre syndrome, presenting with Landry’s acute flaccid
(ascending) paralysis and transverse myelitis.
|2. Miller-Fisher syndrome, characterized by external
ophtalmoplegia, ataxia and areflexia.
|3. Acute disseminated encephalitis and transversal myelitis
during the course of a viral infection.
|It was started corticosteroid, Methylprednisolone was
administrated at a dose of 1 mg/kg intravenous application,
as in the next three days it was carried out pulse therapy with
Methylprednisolone 1000 mg i.v.; intravenous immunoglobulin
in a dose 800 mg/kg, symptomatic treatment - Mannitol,
Nivalin, Milgamma N; antibiotics; unfractionated heparin;
antihypertensive medications. The neurologic abnormalities
ameliorated as a result of the applied treatment – resolution of the cranial nerve lesions, concentrated the sensory disturbances
in the distal parts of the limbs and improvement of the muscle
strenght in the upper limbs.
|The patient’s medical history is notable for an adverse reaction to
HBV (hepatitis B) vaccination when he was 12 years old. Back then
he developed fever, urticaria on the trunk and the limbs, palpable
purpura on the lower legs, myalgias and hepatosplenomegaly.
This episode was followed by acute renal failure, widespread
suffusions, generalized grand-mal type seizures. The skin biopsy
of the lower leg revealed leukocytoclastic vasculitis (perivascular
and mural infiltrates consisting of mononuclear and neutrophil
leukocytes, erythrocyte extravasates, involving the superficial
veules and arterioles). The immunofluorescent staining
demonstrated deposition of IgM, IgA, C4 and fibrinogen in the
vessel wall. A kidney biopsy was also performed with histological
picture of thrombotic microangiopathy. The patient was diagnosed
with thrombotic thrombocytopenic purpura (TTP syndrome,
Moschcowitz syndrome). Thrombotic thrombocytopenic purpura
(TTP) is a rare blood disorder characterized by clotting in small
blood vessels of the body (thromboses). In its full-blown form,
the disease consists of the pentad of [1,2]:
|• Microangiopathic hemolytic anemia
|• Thrombocytopenic purpura
|• Neurologic abnormalities include hemiplegia, paresthesias,
visual disturbance, aphasia and seizures
|• Renal disease, presenting with acute renal failure.
|In the congenital form of TTP, mutations in the gene encoding
the protease ADAMTS13 have been described. ADAMTS13 is a
protease that is responsible for the breakdown of the ultralarge
von Willebrand factor (vWF) multimers. In the more common
sporadic form, antibodies against ADAMTS13 can be isolated
in most patients . The increase in circulating multimers of
vWF increase platelet adhesion to areas of endothelial injury,
particularly at arteriole-capillary junctions [2,3].
|The patient was treated with corticosteroids, plasmapheresis
and hemodyalisis for total of 18 months. The kidney function improved and the dose of the corticosteroid was tapered
to discontinuation. During his teenage years he developed
metaboloic syndrome – hypertension, obesity, hyperuricemia,
impaired glucose tolerance.
|One month after the latest symptoms onset the patient was
admitted to our rheumatology clinic. The physical examination
showed systolic murmur at the heart apex, propagating to the
posterior axillar line, diastolic murmur with punctum maximum
at the aortic valve, propagating to the carotic arteries, bilateral
knee arthritis. The neurological status revealed quadriparesis to
paraplegia for the lower limbs – peripheral type, knee and Achilles
areflexia, tactile hypesthesia in the upper limbs – distal type. The
routine lab studies were notable for high ESR (45 mm), C-reactive
protein (40 g/l), leukocytosis with neutrophillia on background
corticosteroid therapy, high BUN (15 g/l), low grade proteinuria
up to 0.6 g/l. The serum creatinine was normal (67 mkmol/l).
|Given the proven vasculitis in the childhood. a connective tissue
disease was included in the differential:
|1. Polyarteritis nodosa
|2. Systemic lupus erythematosus with involvement of the
CNS presenting as transversal myelitis and disseminated
|Polyarteritis nodosa is systemic necrotizing vasculitis
predominantly affecting the middle-sized muscular arteries .
Given this definition we performed a CT angiography of the
abdomen and pelvis with no signs of stenoses, thromboses or
aneurysms of the abdominal aorta and its branches. Albeit rarely,
PAN could affect the cerebral arteries with resulting ischemia,
haemorrhage and epileptic seizures . Contrast enchanced MRI
of the brain was also performed with no evidence for aneurysms,
stenoses or thromboses of the blood vessels. The only finding was
a gliotic focus of vascular origin, located supratentorially in the
subcortical brain tissue of the left frontal area. An EKG showed
Q-wave in leads II, III, avF – finding that has been persisting
from the childhood. We assumed that the patient may have
had coronaritis due to Moschkowitz syndrome so we performed
echocardiography that revealed pericardial effusion, septoapical
hypokinesia, anterior mitral leaflet prolapse with resulting mitral regurgitation 2nd grade.; aortic regurgitation - 1st grade. A CT
coronarography didn’t find any significant stenoses. A muscular
band of left anterior descending artery was noted. Given the
absence of any changes of the arterial walls, polyarteritis nodosa
was excluded as possible diagnosis.
|It’s possible that transversal myelitis is neurological manifestation
of systemic lupus erythematosus [5-8]. This hypothesis is
supported by the presence of arthritis, thrombocytopenia, lowgrade
proteinuria, pericardial effusion. ANA immunofluorescence
test was done with further typisation of different antibody
specifities – anti-RNP/Sm, Sm, Ro, La, Ro-52, Scl-70, PM/Scl, anti-
Jo-1, anti-Cent. B, anti-PCNA, anti-nucleosomes, anti-histones,
anti-Rib. P – all negative. The complement levels were normal –
C3: 1.85 g/l; C4: 0.35 g/l. The serum level of immunoglobulines
A, G and M were also normal. A lupus band test was performed
– negative. The absence of specific SLE antibodies, anti-platelets
antibodies and the uncertainty about the origin of the kidney
damage made us exlude this diagnosis. The kidney changes may
be a result of the TTP and could explain the low grade proteinuria,
the ultrasound findings of a diffuse parenchymal process.
|We tested the patient for presence of the following antibodies
– anti-proteinase 3, anti-myeloperoxidase, anti-b2-glycoprotein
I, anti-prothrombine, anti-annexin V-IgG, anti-annexin V igM,
anticardiolipin antibodies, rheumatoid factror – IgM, IgA, IgG – all
were negative. The Guillaine-Barre specific antibodies (anti-GM1,
GM2, GM3, GM4, GD1b, GD2, GD3, GT1a, GT1b, Gq1b) were also
|A repeat lumbar punction revealed slightly increased protein –
0.65 g/l (0.15-0.45 g/l), normocytosis.
|Based on the clinical manifestations and the disease course, the
ENMG and MRI data we concluded that the patient has acute
demyelinating polyradiculopathy, Gullaine-Barre syndrome
presenting with ascending paralysis type Landry and transversal
myelitis. We continued corticosteroid therapy with gradual tapering
until reaching a maintenance dose of 8 mg/methylprednisolone
per day. We also administered Nivalin (galantamine), Milgamma
N (benfotiamine, pyridoxine, cyancobalamine). After 9 months of
therapy the patient regained muscle strength in all four limbs,
without any sensory abnormalities.
Figures at a glance
- Bouw MC, Dors N, Ommen HV, Ramakers V, Woerden NL (2009) Thrombotic thrombocytopenic purpura in childhood. Pediatr Blood Cancer 53: 537-542.
- Wun T, Besa EC (2014) Thrombotic thrombocytopenic purpuraMedscape.
- Sauna ZE, Okunji C, Hunt RC (2009) Characterization of conformation-sensitive antibodies to ADAMTS13, the von Willebrand cleavage protease. PLoS One4: 6506.
- Hochberg M (2011) Polyarteritisnodosa and microscopic polyangitis: Rheumatology pp: 1523-1535.
- Hochberg M (2011) Clinical features of systemic lupus erythematodes: Rheumatology (5thedn), Elsevierpp: 1229-1247.
- Lukjanowicz M, Brzosko M (2009) Myelitis in the course of systemic lupus erythematosus. Pol Arch Med Wewn119: 67-73.
- Kovasc B, Laffert T, Brent LH (2000) Transverse myelopathy in systemic lupus erythematosus; an analysis of 14 cases and review of the literature. Ann Rheum Dis 59: 120-124.
- Birnbaum J, Petri M, Thompson R (2009)Distinct subtypes of myelitis in sytemic lupus erythematosus. Arth Rheum 60: 3378-3387.