Acute intramedullary myelopathy


Toxic myelopathy: Can occur hours after intranasal insufflation of heroin.


Drug-induced myelopathy: Anticoagulant drugs may be the cause of epidural hematoma. Clioquinol or anti-TB medication exposure can result in myelopathy.


Primary CNS infections: These include myelitis/abscess and can be caused by legionella, mycoplasma, Chlamydia pneumoniae, Lyme disease (meningomyelitis, MS-like syndrome), brucellosis, TB (radiculomyelitis and infarcts of the cord, PCR testing of CSF is positive in over 50% of cases of TB meningitis), Clostridium tetani (tetanus), Bartonella henselae (cat-scratch disease), neurosyphilis (tabes dorsalis) and fungal infections (both involve basal meninges and cause cranial nerve abnormalities and low glucose in CSF, risk factors for fungal infections). Parasites include: toxoplasmosis, Schistosoma haematobium, Schistosoma mansonii, Schistosoma japonicum, Toxocara spp. Eosinophilia in CSF favors parasitic infestation. Viruses that are tropic for spinal grey matter include poliovirus, retroviruses such as HIV (HIV-associated vacuolar myelopathy) and HTLV-1 (tropical spastic paraparesis), Enteroviruses, mumps, measles, rubella, group B arboviruses (West Nile and dengue), Hepatitis A, B, C, EBV, lymphocytic choriomeningitis virus, herpesviruses such as CMV, HSV-2 and VZV. The latter can cause acute or subacute necrotizing, ascending complete transverse myelitis (one to two weeks after rash, paraparesis with sensory level and bladder dysfunction) and is associated with local swelling and spotty enhancement over several cord segments. CSF may be normal or mild pleocytosis aith elevated protein level may be found. PCR testing has revealed viral DNA and serologic test for varicella is positive. Fungal infections (coccidioidomycosis and histoplasmosis) prevail in immunocompromised patients, organ transplantation, diabetes, or travel to remote tropical locations.


Neuromyelitis optica (NMO, Devic disease): Although mostly sporadic, familial cases have been reported. The disorder affects predominantly young adults, and is clinically characterized by the following criteria:  (1) optic neuritis, (2) acute longitudinally extensive transverse myelitis (LETM), (3) no evidence of clinical disease outside (1) & (2) and (4) NMO -IgG (being anti-aquaporin-4 water channel protein (AQP4)) positivity. Major supportive criteria (and different from MS) are negative MRI at onset, spinal cord MRI with signal abnormality extending over more than 3 vertebral segments and CSF pleocytosis >50 WBC/mm3 or 5 neutrophils/mm3. Minor supportive criteria are bilateral optic neuritis, severe optic neuritis with fixed visual acuity worse than 20/200 in at least one eye and severe, fixed, attack related weakness in one or more limbs. Oligoclonal bands are absent. The disease is either monophasic (13%) or relapsing (87%). Patients with monophasic course usually present with rapidly sequential events (5 days) with moderate recovery. Relapsing cases have extended intervals between events (166 days). One third of the latter die because of respiratory failure. Besides the NMO phenotype, other phenotypes have been identified: bilateral or recurrent optic neuritis, chronic relapsing inflammatory optic neuropathy, relapsing LETM, acute brainstem and hypothalamic syndromes associated with abnormal imaging. Long-term immunosuppressive therapy (induction therapy with steroids followed by maintenance therapy of azathioprine or mycophenolate mofetil. Retuximab is an alternative) is recommended. AQP4 has also been found in SLE, Sjögren syndrome and MG.


Acute disseminated encephalomyelitis (ADEM): This is a subacute monophasic illness.

Postinfectious transverse myelitis: This etiology accounts for almost 40% of cases of acute transverse myelitis. In about 30% of cases there is evidence of preceding or underlying viral or bacterial infection: influenza, adenovirus, mumps, measles, rubella, HSV-1 and 2, VZV, EBV (severe pharyngitis with cervical lymphadenopathy), CMV, HTLV-1 and HIV, enteroviruses, Mycoplasma pneumonia, Lyme disease and syphilis. The manifestations typically progress from a few days to a week. The most typical initial symptoms are bilateral paresthesias and severe localized interscapular or back pain sometimes followed by spinal shock. The sensory symptoms are then followed by leg weakness (initially hypotonia but in a few days changing to spasticity), loss of pinprick sensation and autonomic dysfunction. Depending on the level of the lesion spastic quadriparesis (cervical cord) or flaccid paraparesis (conus medullaris) may develop. CSF shows elevated CSF protein content and a mild degree of pleocytosis. In necrotizing encephalomyelitis red cells and polymorphonuclear cells may be present. There is a diagnostic window for the PCR method in the early phase of VZV infection, after which viral DNA may disappear in the CSF. Spinal MRI shows increased signal intensity on T2 weighted images with or without cord swelling but may be visible only after a few days. Brain MRI should always be performed and differentiates from acute transverse myelitis caused by MS by spinal cord involvement of two or more spinal segments. Signs of recovery are observed a few weeks after the onset of symptoms. Complete recovery is found in 30% of cases. A rapid response to corticosteroids is unusual.

Postvaccination transverse myelitis: Smallpox and rabies vaccination have been associated with this type of myelitis.


Idiopathic acute transverse myelitis (IATM): This form accounts for about 36% of cases of acute transverse myelitis. There is a bimodal peak in the occurrence of IATM: 10-19 years and 30-39 years. The syndrome present as a typical transverse myelopathy. The diagnostic criteria are the following: 1) development of sensory, motor, autonomic dysfunction; 2) bilateral signs or symptoms; 3) clearly defined sensory level; 4) exclusion of extra-axial compressive etiology by MRI; 5) inflammatory signs in the CSF; 6) progression of nadir between 4 hrs and 21 days after symptom onset. MRI may show gadolinium enhancement (38-47%) and CSF pleocytosis or elevated IgG index. Brain MRI should be normal. One third of patients recover with little to no sequelae. Often IATM is associated with systemic rheumatologic disorders. Rapid progression of symptoms, back pain, spinal shock, absent central conduction on evoked potential testing, the presence of 14-3-3 protein in the CSF predict poor outcome. Plasma exchange combined with IV methylprednisolone (1,000 mg for 3-5 days) is more effective than steroids alone.


Multiple Sclerosis (MS): Although MS accounts for about 20% of cases of acute transverse myelitis, it is infrequent the initial clinical presentation of the disease. MS may present as a chronic slowly progressive isolated myelopathy in later life, while in younger adults it may present as an acute or subacute transverse myelitis. Mostly it monosegmental and confined to the cervical cord. Other evidence of MS should be sought: clinical history, oligoclonal bands, abnormal evoked potential and abnormal brain MRI. It can initially be mistaken for GBS, however the presence of pyramidal signs, sensory level on the trunk, asymmetry of the presentation and the presence of oligoclonal bands favor the diagnosis of MS.


Paraneoplastic myelitis: Hodgkin lymphoma


Postradiation myelopathy: The syndrome of delayed radiation-induced myelopathy has bimodal incidence, with peaks at 12-14 months and 25-28 months after completion of radiation therapy. Radiation-induced myelopathy presents predominantly by sensory disturbances and paresthesias, and is not associated with pain. Lhermitte sign is often found. These symptoms are often followed by weakness and frequently sphincter disturbances. Some patients may have severe pain in the lower limbs. Brown-Séquard syndrome and LMN disease are common. This relates particularly to radiation of tumors of the lung, esophagus, and head and neck tumors. CSF findings are atypical. MRI of the spine typically shows abnormally increased T2 weighted images within the affected cord, with sometimes edema. Patients receiving a total dose of 5,000 cGy, or daily fractions of 200 cGy or more are more prone to develop radiation-induced myelopathy.


Systemic diseases: Neurosarcoidosis, Behçet disease, Wegener granulomatosis, Sjögren syndrome, linear scleroderma, MCTD, Hashimoto encephalopathy (myelopathy), PACNS, APLS and SLE. The latter being the most common one.


Acute or subacute necrotizing myelopathy: This is usually not associated with severe back pain. Infarction of the spinal artery or venous thrombosis may develop as complication of either carcinomatous or lymphomatous meningitis or simply as part of atherosclerosis or aortic aneurysm. Initial symptoms may resemble those of radiculopathy.


AVM of the spinal cord or spinal epidural arteriovenous fistula: The clinical presentation is often that of subacute necrotizing ascending myelitis (Foix-Alajouanine). Spinal AVMs are of 4 main types: 1) dural AV fistulas, they are found mainly in the dorsal aspect of the lower thoracic cord and conus medullaris. They consist of a single arterial feeder from the dura that drains into an intradural arterialized vein. These typically affect males between the 5th - 8th decades. Nearly 60% are spontaneous, whereas about 40% are caused by trauma; 2) glomus malformations, these are inside the spinal cord (intramedullary) and consist of a compact vascular plexus which is supplied by multiple feeders from the anterior and posterior spinal arteries. These are usually located dorsally in the upper part of the cord in the cervicomedullary region. They occur most often in younger patients and cause acute onset of symptoms secondary to hemorrhage; 3) juvenile type AVMs, are large, complex vascular masses that involve the cord and often have extramedullary or even extraspinal extension. Multiple arterial feeders from several different vertebral levels are common; 4) intradural extramedullary AV fistulas, these lesions are fed by the anterior spinal artery and lie completely outside the spinal cord and pia mater. These occur in patients in their 3rd – 6th decades. Progressive neurological deficits are typical. Other lesions that may cause a similar picture include venous malformations, capillary angiomas and cavernous angiomas. Hematomyelia is a frequent complication of AVM. CSF may indicate impairment of the blood brain barrier (increased total protein and Q-albumin with normal CSF albumin and IgG). In general, the majority of affected patients are males older than 50 years of age. About half of the patients have an acute onset of pain and dysesthesia or may complain of intermittent sciatica. Patients may have a full blown myelopathic picture or may have transient weakness and sensory disturbances followed by progressive radiculospinal symptoms. There may also be bowel or bladder incontinence and impotence. Myelography, MRI of the spinal cord and spinal angiography may provide the diagnosis.


Angioma of the cord: Occurs in young patients and is often associated with SAH and apoplectic presentation.



Acute extramedullary myelopathy


Spinal cord compression: primary (lymphoma), secondary (multiple myeloma) and metastatic leptomeningeal neoplasms, epidural hematoma, epidural abscess, intervertebral disc herniation, aortic dissection or AVM are the commonest causes of spinal cord compression. PCR of CSF may be useful in lymphoma to detect rearrangement of Ig or T-cell receptor gene


Intervertebral disc herniation:


Spinal metastatic disease: Focal tenderness of the spine and signs of myelopathy strongly indicates acute cord compression caused by epidural metastatic process. The most common neoplasms causing epidural metastases include carcinomas of the lung, breast, prostate (elevated prostate-specific antigen) and kidney, lymphoma and sarcoma. Most metastases occur in the thorarcic spine and nocturnal pain is quite common. Spinal MRI is the most useful diagnostic procedure.


Carcinomatous meningitis: Spinal cord compression or polyradiculopathy can both be caused by carcinomatous meningitis. Lymphoma, leukemia, adenocarcinoma and melanoma often result in carcinomatous meningitis. CSF shows mild pleocytosis, reduced glucose and raised protein. Oligoclonal bands are found and cytology is positive.


Epidural hematoma: This is more likely to be seen in patients with anticoagulant therapy.


Epidural abscess: Similarly to brain abscesses, the triad of fever, back pain and neurological deficit is very suggestive for an epidural abscess. Patients with epidural abscesses often have risk factors for chronic bacteremia, including iv drug abuse, endocarditis, long-term presence of indwelling catheter, or medical conditions that compromise resistance to infection, such as diabetes, alcoholism, immunodeficiency state or cancer. Thoracic or lumbar epidural abscesses are more common than cervical ones. Bacteria can also spread through the intervertebral disk, causing diskitis, secondary osteomyelitis and finally an epidural abscess. The most common bacteria are Staphylococcus aureus and gram-negative bacilli. Therapy should initially consist of ceftriaxone, vancomycin, metronidazole and dexamethasone.


Spinal fractures



Subacute/Chronic myelopathy



Subacute necrotizing ascending myelitis (Foix-Alajouanine): This disorder represents a specific type of subacute/chronic radiculomyelopathy of adult men characterized by amyotrophic paraplegia that runs a progressive course over several months. Early spastic paraplegia evolves aftyer a few weeks or longer into flaccid, areflexive one. Sensory loss and sphincter disurbance follow the paresis. CSF protein is elevated but cells are normal. The course is aggressive.


Noninfectious inflammatory disorders: Neurosarcoidosis, PAN, Behçet disease, Sjögren syndrome, MCTD (Raynaud’s phenomenon, arthralgia, myositis, SLE–like skin changes, esophegal constriction, speckled ANA >1/1280, anti-RNP antibodies >1/1800 and positive RF), granulomatous angiitis, APLS and SLE. SLE being the most common one. Sjögren syndrome usually involves the spinal cord, with clinical, CSF, and MRI abnormalities that may resemble those of MS. It affects usually woman, and a sicca complex is found. Angiitis with thrombosis and incomplete infarction of the thoracolumbar segments associated with SLE can also cause an acute transverse myelitis or resemble MS. In rare cases granulomatous angiitis presents as an acute ascending, or progressive transverse myelitis, often with pain. The disorder may be associated with immune disease or sarcoidosis and Hodgkin disease. Neurosarcoidosis causes in 30% isolated intramedullary lesions. The CSF is usually nonspecific: glucose may be low, IgG index is increased and oligoclonal banding is present in over 30% of patients. Serum ACE is elevated (>52 U/L) in 66-83% of patients with active neurologic disease (false positive with TB). In CSF, ACE is elevated in 55% of patients (false positive malignant tumors). Ratio CD4+/CD8+ is increased in CSF. MRI findings include diffuse cord enlargement and an increased signal over the cervical and thoracic spine on T2 weighted images. Transbronchial lung-biopsy or mediastinoscopy with biopsy is usually required to confirm the diagnosis. IHCPM, pachymeningitis resulting from intracranial hypotension may result in dural pachymeningitis. Occasionally rheumatoid pachymeningitis, syphilis, TB  cancer and Wegener granulomatosis may cause dural involvement with meningeal irritation.



Hereditary diseases: MLD, X-AMN, KLD, HSP, GM2 ggld, HSD and arginase deficiency.


Degenerative ostheoarthritic disease: spinal stenosis


Syringomyelia: Ependymomas, astrocytoma, and hemangioblastomas are the most common tumors associated with a syrinx.


Expanding tumor of the central cord: Intradural tumors are e.g. pilocytic ependymoma (expand over many segments and contain cavities), spinal astrocytoma, hemagioblastoma, leukemia, and lymphoma. Spinal astrocytoma are commonly observed between the age of 35-40 years. The tumor is frequently associated with a syrinx (up to 40%). Five-year survival is 50%. Spinal cord ependymoma occurs commonly between the age of 35-45 years. Five-year survival is 85%. Hemangioblastoma is typically an adult tumors and becomes symptomatic during the 3rd - 5th decades. Hemangioblastomas associated with VHL syndrome frequently present earlier, usually in the 2nd - 3rd decades. These tumors are often associated with a syrinx. The first symptoms of intramedullary tumors are often midline backpain or local back pain with or without radicular pain and dysesthesia. Tumors of the lumbar region and conus medullaris frequently present with back and leg pain. Bladder and bowel dysfunction tends to occur early. Bandlike distributions of sensory loss, multiple sensory levels with relative preservation of sacral sensation, and dissociation of pain/temperature from proprioceptive sensory modalities may be clues to the existence of a central cord syndrome. MRI reveals multiple T1 hypointense lesions. If hemangioblastoma is confirmed on pathologic examination, a thorough search for associated neoplasms or other vascular malformations, including retinal examination for angiomas, CNS imaging for undiagnosed tumors or vascular anomalies, and renal ultrasound or CT imaging, is mandatory. Differential diagnosis includes intramedullar metastasis, neurosarcoidosis, demyelinating lesions, schistosomiasis and vascular lesions.


Von Hippel-Lindau syndrome (VHL): This multiorgan system disease is inherited as an autosomal dominant trait but can occasionally arise without a family history.  Cerebellar and spinal cord hemangioblastomas, angiomas of the retina, multifocal and bilateral renal cell carcinomas, pheochromocytomas, islet cell tumors of the pancreas, and multiple cysts of the kidney, pancreas, ovaries, and other organs may appear in any combination or sequence and at any age 2nd and 3rd decades but up to the 7th decade. RBC count is useful to rule out polycythemia, which can be associated with renal neoplasms. If hemangioblastoma is confirmed on pathologic examination, a thorough search for associated neoplasms or other vascular malformations, including retinal examination for angiomas, CNS imaging for undiagnosed tumors or vascular anomalies, and renal ultrasound or CT imaging, is mandatory. If the patient is thought to have VHL, additional testing should include 24-hour urine determinations of catecholamines, metanephrines, or vanillylmandelic acid, as pheochromocytomas are often associated with this syndrome. The gene is mapped to chromosome 3p25-26. Death usually occurs due to renal cell carcinoma.


Extradural compression from tumors: Multiple myeloma cause epidural compression. Other characteristics are hypercalcemia, IgG lambda M component band and moth-eaten appearance of affected bone.


Subacute combined degeneration of the spinal cord (SACD): Vitamin B12 deficiency leads to SACD. High-risk groups for the deficiency syndrome include the elderly, defective intrinsic factor production by gastric parietal cells (pernicious anemia), patients taking ulcer medications over long periods, heavy abuse of nitrous oxide, patients with AIDS, vegetarians, patients who have undergone stomach resection or small bowel resection, or both, and patients with dementia. The onset of symptoms is usually insidious, with paresthesias in the hands and feet present in the majority of patients. Sensory peripheral neuropathy can be the sole manifestation of B12 deficiency. Paresthesias in the feet and distal loss of all modalities of sensation with loss of ankle jerks are observed. Symptoms improve after therapy with B12. The next most common complaints include weakness and unsteadiness of gait. Cerebral symptoms may occur and can include confusion, delusions, hallucinations, mental slowing, and depression. Loss of position or vibration sense is the most common abnormality. Motor impairment may range from only mild clumsiness to a spastic paraplegia. Visual impairment can be seen; ophthalmological exam may show bilateral visual loss, optic atrophy, and centrocecal scotomata. Brainstem or cerebellar signs or even reversible coma may occur. Hematological abnormalities, including hypersegmentation of polymorphonuclear cells and a macrocytic anemia, can be seen; however, they may be completely absent at the time of neurological presentation. Current state-of-the-art testing uses serum cobalamin levels as a screening test, and the Schilling test, serum or urine methylmalonic acid and homocysteine determinations as confirmatory tests. A Schilling test detecting impaired intestinal absorption of vitamin B12, should be performed if there is enough clinical suspicion for the disease, and may reveal low vitamin B12 absorption even when the serum level is normal. The presence of circulating antibodies to parietal cells in many of these patients suggests an underlying autoimmune disorder. MRI reveals confluent leukoencephalopathy, even in the absence of anemia or myelopathy. VEP and SEP are frequently abnormal. SNAPs are absent or reduced in about 80% of patients and motor NCVs show axonal and demyelinating features. A typical regimen consists of intramuscular vitamin B12 injections of 1 mg twice weekly for 2 weeks, followed by monthly injections of 1 mg. For patients whose Schilling test demonstrates malabsorption of vitamin B12, monthly 1 mg injections should be continued on a lifelong basis. There is no evidence that overdosing can speed neurologic recovery; adverse reaction to high doses of vitamin B12 is unknown. Recovery can be complete but may take 3 to 6 months.


Constrictive arachnoiditis:


Dural AV fistula: Often exercise-related pain or numbness of the legs, or both are indicative of this disease. MRI findings include segmental cord edema or myelomalacia, scalloping of the cord, and serpentine vessels with low signal intensity in the subarachnoid space. Spinal arteriography can be indicated.


Chronic infectious disease: Dural pachymeningitis may result from subacute or chronic infections such as TB, syphilis, fungi (candida, aspergillosis and pseudallescheria), schistosomiasis, epidural abscess and cause progressive spinal cord compression. Underlying conditions are almost always present.


Spastic paraplegia, ataxia, mental retardation (SPAR): This autosomal dominant disorder is characterized by either pure spastic paraplegia, spastic ataxia, spastic ataxia with mental retardation and dystonia. MRI shows cerebellar atrophy. It needs to be differentiated from SCA-1-3, 6-8 and 12, DRPLA and HSP.


Neurofibromatosis type 1 (NF-1 or Von Recklinghausen disease): NF-1 is one of the most common neurogenetic diseases affecting adults, occurring in 1/3,000 to 4,500 individuals. The major adulthood features of this autosomal dominant disorder consist of pigmentary lesions (café au lait spots (99%) and skin fold freckling (77%)) as early manifestations. Six or more café au lait spots (uncommon in the face) are essential to diagnose NF1. Nearly all adults with NF-1 will develop neurofibromas at some stage during their lives. Cutaneous neurofibromas particularly in the upper extremities are standard. Trauma or hormonal influence (puberty and pregnancy) may accelerate the growth of neurofibroma. CNS tumors of NF-1 are astrocytomas of the optic pathway, gliomas, spinal neurofibromas and malignant peripheral nerve sheath tumors. Other associated disorders may be AHT, rhabdomyosarcoma, Wilms' tumor and musculoskeletal abnormalities. Chromosome 17q11.2.7 is the site of the neurofibromatosis type I gene. The diagnosis is based on the protein truncation assay. Life expectancy is reduced with 15 years and is predominantly caused by metastatic malignant peripheral nerve sheath tumors.