Differential Diagnosis in Neurology

4.1. Introduction

Spinal Cord Disease

The spinal cord is frequently involved in specific patterns and at characteristic levels that is extremely helpful in differential diagnosis. The lamination of both the dorsal column and the spinal thalamic tracts is such that the patient's symptoms may not reflect the true level of involvement. This is particularly true with sensory levels. Pain afferents enter the cord and are distributed approximately two segments above and below their level of entry by Lissauer's tract. Propriospinal fibers connect adjacent spinal dermatomes. The corticospinal tract is arranged so that the fibers innervating the legs are lateral to those of the arm. Bladder fibers are between arm and leg fibers. The spinothalamic fibers are laminated such that sacral fibers are most lateral and leg, trunk and arm fibers are medial and cross at their level of entry. Thus a lateral cord lesion at cervical levels will affect the contralateral sacral and leg sensory fibers prior to arm fibers.

The clinical and neuropathological division of the cord is into three spaces:

• epidural
• intraparenchymal
• intradural and extramedullary

Processes that compress the spinal cord cause ataxia, a sensory level issue on the trunk, then bilateral motor weakness below the level of the lesion and bladder involvement. If epidural processes are acute, such as metastasis, intradural hematoma or fracture, there will be spinal shock. If this supervenes, all sensation, motor function, bowel, and bladder control and reflexes will be lost below the level of the lesion. Long standing intraparenchymal spinal cord disease causes spasticity below the level of the lesion with a neurogenic bladder. There is a segmental sensory loss with normal sensation above and below the lesions. Occasionally, reflexes will be increased above the level of the lesion (Schiff–Sherrington reflex). This is due to disinhibition of excitatory ascending fibers. Cystic intraparenchymal lesions and tumors often cause minimal bladder dysfunction. Epidural compression affects bowel, bladder and then ability to walk, rarely ataxia present initially. Predominantly as the dorsal and ventral spinocerebellar tracts are in the periphery of the cord and they both subserve cerebellar functions of the legs. The patient is ataxic prior to becoming paralyzed. The cuneocerebellar tract conveys proprioception from the upper extremities and is located at cervical levels C1–C4. Proprioceptive loss has to be sought by the examiner, although there is frequently a lateral drift of the ipsilateral extremities.

Intradural extramedullary lesions are few and comprise meningiomas, neurofibromas, dropped metastasis and enlarged nerve roots from congenital hereditary motor sensory neuropathies. If a neurofibroma or meningioma occurs in the thoracic or cervical area there is often concomitant root and spinal cord compression. In the lumbar area, roots are involved as the spinal cord ends at T12–L1 (conus medullaris).

Differential diagnosis of spinal cord pathology depends on location and pattern of involvement as well as the course of the process.

Specific Patterns of Involvement

• Transverse (in fact these are usually longitudinal)
• Longitudinal hemisection (Brown–Sequard syndrome)
• Epidural compression
• Intramedullary (usually inflammatory or tumor and cause a longitudinal lesion on MRI)

The specific diagnostic radiographic features for these patterns are:

• Transverse myelitis involves more than one segment and expands the spinal cord. If involvement is more ventral a viral etiology is expected. Dorsal column involvement that suggest Sjögren's, B12 deficiency, Tabes dorsalis or toxins.
• Brown–Sequard: This is a longitudinal division of the cord. The patient suffers ipsilateral proprioceptive, touch and vibratory loss in association with contralateral pain and temperature deficits. There is ipsilateral paralysis below the lesion. The usual etiology is trauma (knife or bullet) or X-RT therapy in which individual sulcal arteries are involved.
• Intramedullary: The cord is swollen over several segments in an ovoid pattern. Central or asymmetric cysts suggest a syrinx. A post traumatic syrinx occurs above the level of the lesion. Tumors that are associated with intramedullary syrinxes are cystic astrocytomas (frequently an enhancing nodule is seen), hemangioblastomas as well as astrocytomas that occur in the wall of syrinxes.
• Epidural compression: A saw-toothed or paint brush pattern on myelography is seen with epidural processes. Bony destruction suggests metastatic disease. This is often only at one segment. Disc involvement, with gadolinium enhancement, denotes infection. The anterior and posterior ligament often enhance with gadolinium with infection. Lymphomas often start in the epidural fat. Epidural compression is noted with extra medullary hematopiesis, as well as by fat in patients on steroids. Dural AVMs are epidural and are most common dorsal in the thoracic segments of the cord. Meningitis of all forms may be dorsal and invades the spinal parenchyma through draining veins or exit foramina. Sarcoid often invades the dura at cervical and thoracic levels. Processes that thicken the spinal dura itself are lymphoma, tuberculosis, cryptococcus; rheumatoid arthritis and idiopathic pachymeningitis which simultaneously affect intracranial dura. Carcinomatosis of the meninges characteristically thickens the dura and is seen in the sulci of the cerebellum and cortex. Angioplastic endotheliosis may affect cerebral blood vessels and those of the dura. Amyloid may greatly thicken the dura of intracranial and spinal compartments and occasionally forms mass lesions.

Intradural Extramedullary Lesions

The most common of these are Schwannomas that form "dumbbell tumors". The neuronal exit foramina are expanded and the tumor is seen to compress the spinal cord. Myelography reveals a "cap" sign. Neurofibromas grow through the nerve root, as opposed to Schwannomas which can be separated from the nerve root. Plexiform neurofibromas may involve multiple nerve roots and are characteristic of neurofibromatosis type I (chromosome 17). Hereditary motor sensory neuropathy particularly Dejerine–Sottas disease (HSMN III) greatly enlarge nerve roots and may compress the cord. Meningiomas characteristically are found in the intradural extramedullary space of the thoracic cord in women and are extremely rare in men. A free fragment of a disc may migrate in this space for several cord segments, while arachnoid cysts may fill, in a ball valve fashion, and compress the spinal cord intermittently. Prior to MRI this process was often misdiagnosed as multiple sclerosis. Medulloblastomas, spinal cord, metastases and leukemia frequently seed the spinal cord in the intradural extramedullary space. Spontaneous, traumatic and anticoagulation induced subdural hematomas of the spinal cord also occur here.

Locations

The area of the spinal cord involved is a major clue in the differential diagnosis. The examination is quite specific for each entity. A forward flexed neck with limitation of movement to the lateral planes suggests cervical spondylosis. Degenerative changes in the spine occur at movement segments such as C5–C6, C4–5, while C8–T1 is not affected. All patients above 40 years of age get some degree of cervical spondylosis. The exam will often demonstrate an inverted radial or inverted supinator reflex, increased knee jerks, as well as inability to tandem walk due to lateral pressure on the dorsal and ventral spinocerebellar tracts. A short neck suggests Turner's syndrome, platybasia, Chiari malformation or abnormalities of C1–C2, basilar invagination or Klippel Feil syndromes. There are five ossification centers of C2, and anomalies and fractures occur in these areas. A long neck is suggestive of the "droopy shoulder syndrome" and brachial plexus traction injuries, but may also be associated with homocystinuria, Marfan's or Ehlers Danlos syndrome. Lhermitte's sign is most often associated with demyelinating disease, but also occurs with any lesion that irritates the dorsal columns.

Characteristic pathology involving the cervical cord includes HIV infection and B12 myelopathy (both give a vacuolar myelopathy) Sjögren's syndrome, as well as, spondylosis, disc disease, stenosis, and demyelinating disease. This is very frequently associated with a dropped sensory level to T4–T6 due to lamination of the sensory systems of the spinal cord. A level here invariably draws an MRI at this level, but most often pathology will be at cervical levels. Hirayama's disease, abnormal movement of the cervical spinal cord with consequent pathology at C8–T1, and calcification of the posterior longitudinal ligament with cord compression is common in Asian patients. Syrinxes and cavernous hemangiomas are common parenchymal lesions although demyelinating inflammatory lesions are by far the most common. Rarely will sarcoid present with both inflammatory and dural lesions at this level. A ventral AVM of the anterior spinal artery, the "Foix Alajouanine syndrome" lesion, can be found from cervical to thoracic areas.

Thoracic Spinal Cord

Inflammatory lesions at this level are usually demyelinating, but sarcoid may thicken the dura here as well as inflame the cord. Dural AVMs, if spinal, are most common in the dorsal cord. Disc disease is rare, but protrusions here are very dangerous, as the spinal canal is tight (12–24 mm) and the cord is easily compressed. Diabetes, a syrinx and amyloid may destroy propioceptive and pain fibers which produce a "Charcot joint". This is more common at the shoulder joint, particularly for a syrinx. Metastatic disease with a pathologic fracture and meningioma in women are characteristic. Osteoporoses with anterior vertebral body fractures are most common in elderly women at this level. Ganglioneuromas and chordoma, Weing's sarcoma are rare tumors of the thoracic cord. An astrocytoma may grow a long distance and destroy anterior horn cells of the thoracic spine asymmetrically giving rise to a "C" form of scoliosis. An "S" shaped scoliosis is congenital (with compensatory curves) and is often asymptomatic. Diastematomyelia, a fibrous band that splits the spinal cord, and reduplication of the cord (two spinal cords with their own dural cover) are rare congenital anomalies. A devastating infection of the thoracic spinal cord is herpes type 6, which leads to necrosis with minimal recovery. West Nile virus, as well as polio, may severely affect this part of the cord, but not to the same degree. Axonal necrosis of the cervical cord with optic neuritis (Devic's) disease is more common in the cervical cord, but does occur in the thoracic cord as well.

The many forms of hereditary spastic paraparesis affect the thoracic cord severely. In uncomplicated variants, only the spinal cord is affected while complicated variants are also associated with optic, cerebellar, cortical and peripheral nerve deficits.

Lumbar

The lumbar level is most affected with mechanical problems such as disc disease, spinal stenosis, spondylolisthesis and spondylosis. In general, L5–S1 (the major motion segment) suffers disc disease, while L4–L5 is more frequently the site of spinal stenosis. Synovial cysts of the facet joint are rare, but are often seen in older patients with severe degenerative disease. Facet hypertrophy with tropism (rotation of the inferior facets into the foraminal exit zone) is a common cause of radiculopathy in older patients.

In adult populations, meningomyelocele and its variations are rare. A tethered cord, in which the filum terminal is short and the spinal cord is lower than its usual vertebral level at L1, is associated with bladder abnormality, pes cavus and radiculopathy. An abnormally formed lamina or pedicle often is associated with radiculopathy at this level. The lateral recess, particularly at L4–L5 and L5–S1, may be congenitally narrowed with nerve root compression.

Lipoma, glioma of the filum terminale, and chordomas are particular to the lumbosacral cord. Lymphomas may occur anywhere in the spine, but tend to envelop the nerve roots of the cauda equina at this level. Sarcomatous degeneration of a lipoma cannot be operated, as it is interdigitated within the nerve roots. Plexiform neurofibromas (NFI) occur in the lumbosacral cord.

Patients with CMV infections in very ill (CD4+ count of less than 200 mm³) HIV patients are characteristic of the lumbosacral cord.

Epiconus

Anatomically, this area is at a spinal level T12–L1 and affects the lower end of the spinal cord segment above the conus medullaris which comprises S1–S5. Lesions here cause involvement of the bowel, bladder and sexual function as well as pain and weakness. A Babinski sign is present.

Trauma, congenital defects, such as spinal stenosis in achondroplasia, demyelinating disease or a syrinx may be prominent pathology at this level.

Conus Medullaris

The hallmark of lesions here is the early involvement of bowel, bladder, and sexual function without loss of sensation or weakness. The cauda equina and epiconus are often concomitantly involved. The most common pathologies are trauma, demyelinating disease, vascular malformation, syrinx and, rarely, a tumor. Characteristic of a parenchymal tumor is weakness of the gastrocnemius muscle with spared anterior tibialis and extensor hallucis longus muscle function. Sexual dissociation may also occur whereby a patient may have an erection, but is unable to ejaculate or vice versa.

Cauda Equina

The cauda equina comprises of the nerve roots that have exited the lumbosacral spinal cord. A cauda equina lesion produces asymmetric severe pain, numbness in the perineal or "saddle distribution" and weakness of the lower extremities. Bladder, bowel and sexual function are affected.

The usual pathology of a cauda equina lesion is disc disease, trauma or metastasis.

Spinal Block

In the past, spinal block was most often seen by myelography. The characteristic brush like defect of the contrast column in epidural disease and the meniscus sign of an intradural extramedullary lesion were carefully sought. The block is due to obstruction of the passage of spinal fluid. MRI now allows visualization of water in discs, as well as inflammation and swelling of nerve roots (gadolinium enhancement), while CT allows exquisite detail of the bony exit foramina. The advantage of a myelogram with CT to following is the ability to visualize the relationship of the nerve root both to the pedicle and within its exit foramina. A far lateral disc cannot be visualized with myelography.

A spinal block causes a Freund's reaction in which the protein is very high, while cells and sugar remain normal. A CSF protein of one gram suggests a block as few diseases can raise a protein to this level. The usual protein of an autoimmune process is 80–120 mg%. Deep fungus infections such as blastomycosis may raise the protein to 1 gram/dl, but this is very rare. Most spinal blocks are caused by epidural tumors. Degenerative disc disease is easily seen by desiccation and less signal on T2 weighted MRI images. A lesion in the pedicle or one eroding the end plates of the vertebral body is most often metastatic. A star vertebral fracture may protrude a bone fragment into the spinal canal and cause a spinal block.

Anatomical–Clinical Correlations

• Dropped sensory levels:
  • Thoracic compression causes a dropped sensory level of about two segments. The posterior level is usually slightly higher than the anterior level.
  • Cervical cord lesions cause a dropped sensory level of many segments. As noted above, this is due to the lamination primarily of the spinothalamic tract.
  • A lateral drift and severe proprioceptive loss suggest dorsal column tract or nuclei involvement.
• Motor deficits:
  • In general, spinal cord lesions cause bilateral motor deficits which may be asymmetrical. X-RT characteristically does this by producing a proliferative end arteritis of a sulcal artery. Another cause of asymmetrical motor weakness includes trauma specifically knife or bullet wounds. Most blunt trauma to the cord causes an oblong longitudinal lesion.
• Bladder involvement may have characteristic features depending on the level of involvement.
  • Cervical cord (long standing):
    • Frequency and urgency
    • Loss of urine with a valsalva maneuver. The lesion is often at the ciliary nucleus of Budge at the C8–T1 level and is most often a syrinx.
    • Inability to initiate micturition in the face of urgency. Detrusor dyssynergia is most often seen with demyelinating disease.
  • Thoracic cord (long standing):
    • Urgency, frequency, small amounts voided
    • Detrusor dyssynergia. There has to be coordination between contraction of Onuf's nucleus (S2–S4) and the external sphincter (L5–S1).
  • Lumbar cord:
    • Frequency (often irritation of L5–S1 roots)
    • Incomplete emptying of the bladder (30–40 cc residual) stimulates the trigone. Incomplete emptying with large residuals (>300 cc) causes overflow incontinence. Severe infections such as tabes dorsalis and CMV can affect the roots and cause failure of bladder contraction as well as insensibility. Severe neuropathies such as diabetes and toxins are also noted as causes of an overflow bladder.
• Conus Medullaris:
  • Severe inability to contract the detrusor muscle. This does not occur with ALS as Onuf's nucleus does not degenerate. In many multiple system atrophies, glial inclusions are seen in this nucleus which is occasionally reflected as incontinence.
  • Bladder retention with constant overflow incontinence
• Ataxia of the Legs:
  • Often an overlooked complaint with external compression of the spinal cord.
  • Caused by pressure on dorsal and ventral spinocerebellar pathways which occupy the lateral components of the spinal cord
  • Over shadowed by leg weakness
• Mass reflex with long standing spasticity:
  • Flexion withdrawal (spontaneous or stimulus induced)
  • Defecation
  • Urination
  • Rarely reflex erection and ejaculation
  • Usually often spinal cord injury
• Lhermitte's sign:
  • Dorsal column irritation most often, but not limited to the cervical cord
  • Paresthesias may be felt in the arms, legs or straight down the spinal column
• Sacral sensory sparing:
  • Occurs with central cord lesions: tumors, syrinx, demyelinating disease
• Thoracic-abdominal signs:
  • Beevor's sign, thoracic umbilical reflex, superficial umbilical reflex; intercostal contraction with breathing-all help to localize a lesion at the thoracic level. Unilateral segmental sweating has been noted with thoracic lesions. Severe segmental dynamic and static allodynia is often associated with HZ that presents without rash ("sine herpeticum"). Rarely tabes dorsalis causes shooting thoracic and abdominal pain as do the neurological causes of porphyria. The most commonly missed thoracic nerve lesion is the intercosticobrachial nerve that is derived from the medial cord of the brachial plexus. The upper component of the nerve innervates the anterior chest wall while the lower component subserves the lateral chest wall and radiates under the breast to the epigastrium.

Cervical Drifts

A lateral drift of the outstretched upper extremities may be seen with cervical cord lesions (decreased proprioception from the cuneocerebellar tract). Severe updrift with ataxia through all components of movement in association with polyminimyoclonus (abnormal finger movements) is characteristic of dorsal column nuclear lesions from Richter's variant of GBS or DRG large neuropathies.

Babinski Sign

If the sign is elicited by stroking just to the midfoot, the pathology is either very long standing or in the spinal cord.

The toe is frequently spontaneously extended. Severe basal ganglia disease may give a dystonic extensor plantar response.

Segmental Atrophy

This sign is most often seen with intramedullary lesions such as a syrinx. The patient may be anesthetic in this area due to destruction of the dorsal horn.

Fasciculations

The more fasciculations noted, the closer the lesion is to the anterior horn cell.

Crossed Adductor Reflex

This implies a deficit of spinal cord inhibition. When noted, the patient is suffering from long standing cervical or thoracic cord disease. It may, of course, be seen in any long standing corticospinal tract lesion.

The Clavicular Biceps Reflex

Striking the clavicle and obtaining a hyperactive biceps reflex allows the examiner to note that the lesion must be above C5–C6. (If there is hyperreflexia of the jaw jerk, the process is most likely diffuse and degenerative. A hyperactive jaw jerk means disinhibition of the mid pons). The inverted radial reflex and supinator reflex are characteristic of C5–C6 cervical cord lesions.

Cape Sensory Loss

Decreased sensation of the trapezius ridge, cap of the shoulder and anterior chest wall is strong evidence for a syrinx or other intramedullary lesion.

Dissociated Sensory Loss

Dorsal column modality loss that occurs acutely suggests infarction of the paired posterior medullary arteries. Loss of pain and temperature occurs with ventral cord (anterior spinal artery) or anterior commissure lesions such as a syrinx, intramedullary tumor, demyelinating disease, or compression from a disc.