This site welcomes original publications, review articles, case records in the field of neurology, psychiatry, neuroradiology, neuropathology, and neurosurgery
The author: Professor Yasser Metwally
http://yassermetwally.com
INTRODUCTION
March 7, 2010 — Radiological quiz
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References
March 6, 2010 — Thyroid ophthalmopathy is characterized by inflammation, congestion, hypertrophy, and fibrosis of the orbital fat and muscles leading to enlargement of tissue, especially the extraocular muscles. The extraocular muscles are enlarged, firm, rubbery, and dark red. The histologic findings,that are related to the severity and stage of the disease, consist of interstitial edema and inflammatory cell infiltrates. The inflammatory cells are composed of lymphocytes, plasma cells, and occasional mast cells (B lymphocytes in 80% and T lymphocytes in 20%). The inflammatory reaction, predominantly in the muscle, can also occur in the tendons. The inflammatory reactions are predominantly localized in the endomysial connective tissue with extension to the perimysium and epimysium surrounding the extraocular muscles in the late stage. There is a fibroblast reaction with production of mucopolysaccharides, specifically, hyaluronic acid, characterized by glucose aminoglycons. In the later stages of severe ophthalmopathy, there is fibrosis and fatty infiltrations of muscles resulting in a restrictive myopathy. In general the most common findings in Graves’ disease are extraocular muscles enlargement and expansion of the orbital fat.
Figure 1. Thyroid ophthalmopathy (Click to enlarge figure)
The diagnosis of Graves’ disease is often established by clinical means. CT is the preferred imaging modality for the evaluation of Graves’ disease in cases where the diagnosis is uncertain. Furthermore, CT is used to assess extra-ocular muscle enlargement, fatty expansion, and optic nerve compression, especially prior to surgery and as a follow-up after treatment. This examination should be carried out with 4- to 5-mm-thick sections in the axial and coronal planes. This allows detailed assessment of extraocular muscle enlargement, which provides the most important parameter in the diagnosis. The enlarged muscles are spindle- shaped with the belly reflecting the muscular portion and the tapered, anterior end, the tendinous portion. Occasionally, the muscular tendons may be slightly enlarged. On MR imaging, the normal muscle is characterized by low signal intensity on the Tl-weighted images and intermediate signal intensity on the T2- weighted images. There is marked enhancement of the extraocular muscles following the introduction of gadolinium, which is in contrast to muscles in other body parts, which reveal no enhancement. This is based on the increased vascularity of the extraocular muscles, allowing for diffusion of contrast material into the muscular tissue.
Figure 2. Sever enlargement of the extraocular muscles. (Click to enlarge figure)
It has been shown that increased extraocular muscle volume correlates with severity of optic neuropathy and, furthermore, improvement of the optic neuropathy appears to correlate with decrease in extraocular muscle swelling at the apex of the muscle cone. Significant enlargement of the medial rectus muscle may lead to remodeling of the lamina papyracea with deviation medially from pressure by the medial rectus muscle.
Figure 3. A case of graves disease showing bilateral medial and lateral rectus enlargement. (Click to enlarge figure)
In Graves’ disease, a single muscle may be enlarged such as the medial , inferior and superior rectus muscles. If only axial images are performed, superior and inferior muscle enlargement is easily overlooked and is, therefore, optimally evaluated with coronal sections. Multiple muscles are usually enlarged in Graves’ disease and, not infrequently, both orbits are involved. Sometimes, the patient demonstrates clinical Graves’ disease in one orbit but on the CT study the asymptomatic orbit also reveals enlargement of muscles.
The margins of the muscles are usually well defined. In order of frequency, the inferior rectus is the most common muscle involved in Graves’ ophthalmopathy followed by the medial rectus muscle, and the superior muscle complex composed of the levator-palpebral, and superior rectus muscles. In addition, there is enlargement of the superior oblique muscle, which is optimally demonstrated in the coronal projection.
Figure 4. A case of graves disease showing bilateral medial and lateral rectus enlargement. (Click to enlarge figure)
The lateral rectus muscle often reveals some enlargement in conjunction with the other extraocular muscles, but this is less pronounced and in most cases the muscle appears normal, whereas the medial and inferior rectus muscles reveal enlargement. The degree of muscle enlargement varies from mild to severe with a significant portion of the orbit obliterated when the muscles are markedly enlarged. Significant muscle enlargement leads to bunching in the apex of the orbit with extrinsic pressure on the optic nerve and consequent loss of vision and field defects.
Figure 5. A case of graves disease showing bilateral medial rectus enlargement. (Click to enlarge figure)
Figure 6. CT scan axial and coronal views (graves ophthalmopathy) showing enlargement of the extraocular muscles, notice that the inferior rectus and superior oblique muscle enlargement could only be appreciated on the coronal views. (Click to enlarge figure)
The second most common finding in Graves’ disease is expansion of the orbital fat. This is difficult to quantify on CT, but is suspected in patients with moderate to marked exophthalmus. Fatty expansion leads to considerable stretching and straightening of the optic nerve. Normally, the nerve is undulated when the globe is in a normal position. Frequently, there is a bulge of the orbital septum anteriorly secondary to extrinsic pressure from the expanded orbital fat. Occasionally, there are increased mottled densities within the orbital fat that, on biopsy, have proved to be lymphocytic infiltrations. Some vascular congestion may also contribute to a slight increase in soft tissue densities within the orbital fat, especially if they are linear in configuration. Slight enlargement of the lacrimal glands is also encountered in patients with Graves’ disease, which is well demonstrated on axial and coronal CT images. Rarely, there may be some slight enlargement of the optic nerve, probably the result of lymphocytic infiltrations in the surrounding orbital fat.
Several other disease entities may be responsible for enlargement of the extraocular muscles and, therefore, enter into the differential diagnosis ; these include:
March 2, 2010 — Guided to the location of entrapment by the clinical and neurologic examination, MR imaging is used to detect objective imaging findings of nerve compression (7). Some of the peripheral nerves that are affected and the sites of entrapment include the median nerve in the carpal tunnel (1, 4), the ulnar nerve in the cubital tunnel (3, 5) or in Guyon’s canal, the lower trunk of the brachial plexus at the insertion of the anterior scalene muscle on the first rib (scalenus anticus syndrome) or at the crossing of a cervical rib (cervical rib syndrome) (6), the sciatic nerve at the greater sciatic foramen (piriformis syndrome), and the lateral femoral cutaneous nerve near the attachment of the inguinal ligament to the anterior superior iliac spine (meralgia paresthetica) (2). Compressive neuropathy or plexopathy may also result from hematoma or aneurysmal formation in certain locations: iliopsoas hematoma causing femoral neuropathy or lumbar plexopathy, depending on the extent of hemorrhage, and aneurysm of the abdominal aorta, internal iliac, or gluteal arteries causing lumbosacral plexopathy. Currently, the presence of localized abnormal T2 signal of the involved nerve on MR images has been the most reliable finding and is useful to confirm the clinical diagnosis, to eliminate the possibility of a mass lesion, and to help with surgical planning and postsurgical follow-up.
Since the 1980s, there has been a dramatic increase in the diagnosis of carpal tunnel syndrome (CTS), to the point where it is now recognized as the most common peripheral nerve entrapment syndrome, with an annual incidence of 50 to 150 cases per 100,000 individuals. CTS results from compression of the median nerve in the carpal tunnel . Patients develop insidious onset of paresthesias or numbness in a median nerve distribution in the hand. Pain is frequently present in the hand or wrist and may include the forearm, upper arm, or shoulder. Patients may complain of dropping things from their hands, most likely because of numbness, because weakness of the abductor pollucis brevis and opponens muscles is an uncommon and late finding. Symptoms are usually intermittent and provoked by flexion of the wrist while asleep, repetitive wrist movements, keyboard typing, prolonged wrist flexion or extension, or driving. Symptoms usually improve by shaking the hands, which is in itself a diagnostic test called the “flick test.” [8]
Figure 1. The carpal tunnel (Click to enlarge figure)
Most cases of carpal tunnel syndrome are either idiopathic, especially in the older population, or related to repetitive wrist movements, particularly in young adults. Various medical disorders may predispose individuals to this condition, however (Box 1). Acute or remote wrist trauma may lead to compression of the median nerve. Reduction of the carpal tunnel space available to the median nerve, leading to nerve compression, may occur in several disorders. Diseases associated with polyneuropathy, such as diabetes mellitus or renal failure, also leave the median nerve vulnerable to compression.
Box 1. Causes of carpal tunnel syndrome
Repetitive wrist activities
Idiopathic (increased frequency with increasing age)
Nerve susceptibility to compression
Amyloidosis
Concomitant mononeuropathy multiplex
Concomitant polyneuropathy
Diabetes mellitus
Hereditary neuropathy with liability to pressure palsy
Multiple myeloma
Renal failure
Reduced carpal tunnel space
Acromegaly
Anomalous muscles or tendons
Congenital small carpal tunnel
Generalized edema
Gout
Hypothyroidism
Mass lesions (eg, cyst, ganglion, lipoma, neurofibroma, or other tumors)
Mucolipidoses
Mucopolysaccharidoses
Osteophytes
Pregnancy
Tenosynovitis (eg, rheumatoid arthritis)
Wrist trauma
Acute fracture
Dislocation of the wrist or hand joint
Hematoma
Remote fracture
Swelling
Familial CTS
Various MR imaging findings have been described in patients who have carpal tunnel syndrome. These findings include the following: high signal on T2-weighted images, swelling of the nerve either proximal or distal to the point of maximal compression, flattening of the nerve within the tunnel, bowing of the flexor retinaculum, and thickening with increased signal of the flexor tendon sheaths and deep palmar bursa.
In addition to signal, MR imaging readily depicts nerve configuration. Frequently, the point of maximal compression within the carpal tunnel is at the hook of the hamate, where the cross-sectional area of the tunnel is usually smallest. The compressed nerve is usually swollen proximal to the point of maximal compression, and a dramatic change in caliber often indicates the site of entrapment. When nerve swelling occurs, there is usually prominence of the fascicular pattern, which is best seen on T2-weighted images
In patients with flexor tenosynovitis, axial MRI demonstrates bowing of the flexor retinaculum. Inflamed synovium and tendon sheaths demonstrate low signal intensity on T1-weighted images and increased signal intensity on T2-weighted, T2*-weighted, and short tau inversion recovery (STIR) sequences.
Regardless of the etiology of carpal tunnel syndrome, changes in the median nerve are similar and include the following:
1- Diffuse swelling or segmental enlargement of the median nerve may be demonstrated (usually seen best at the level of the pisiform). 2- The median nerve may flatten (usually demonstrated best at the level of the hamate). 3- Palmar bowing of the flexor retinaculum may be noted (usually demonstrated best at the level of the hamate). 4- Increased T2-weighted signal intensity within the median nerve occurs, which is demonstrated best on axial fast spin-echo (FSE) T2-weighted images. If FSE signal sequences are not available, axial gradient-recalled echo (GRE) or inversion recovery (IR) sequences also are sensitive to the increased edema in the median nerve that accompanies carpal tunnel syndrome.
1- Diffuse swelling or segmental enlargement of the median nerve may be demonstrated (usually seen best at the level of the pisiform).
2- The median nerve may flatten (usually demonstrated best at the level of the hamate).
3- Palmar bowing of the flexor retinaculum may be noted (usually demonstrated best at the level of the hamate).
4- Increased T2-weighted signal intensity within the median nerve occurs, which is demonstrated best on axial fast spin-echo (FSE) T2-weighted images. If FSE signal sequences are not available, axial gradient-recalled echo (GRE) or inversion recovery (IR) sequences also are sensitive to the increased edema in the median nerve that accompanies carpal tunnel syndrome.
MRI also is useful in detecting and characterizing space-occupying lesions, such as neuromas, ganglion cysts, lipomas, and hemangiomas. Enlargement or swelling of the median nerve proximal to the carpal tunnel, termed a pseudoneuroma, has been documented using MRI.
Figure 2. Cross-section of the wrist obtained by Magnetic Resonance Imaging (MRI), showing the bones and soft tissues in great detail. A build-up of pressure in the wrist can lead to compression of the median nerve (seen as a medium-grey, oval structure) causing carpal tunnel syndrome – pain, a tingling sensation and numbness in the fingers. Indices of nerve compression are measured from the MRI scans. (Click to enlarge figure)
Flow-sensitive sequences or dynamic contrast-enhanced MRI can detect a circulatory disturbance causing carpal tunnel syndrome, which is a cause separate from deformation or compression of the median nerve.
Figure 3. Carpal tunnel: Normal findings of isointense-to-hypointense appearance of the median nerve on fast spin-echo T2-weighted MRI (arrow). Note the fairly well-defined nerve fascicles within the median nerve sheath. (Click to enlarge figure)
One of two abnormal patterns of median nerve enhancement is usually demonstrated: marked enhancement of the nerve (attributed to hypervascular edema) or noticeable lack of enhancement (attributed to nerve ischemia).
Figure 4. Carpal tunnel syndrome. Axial fast spin-echo T2-weighted MRI with fat saturation. Note the increased T2-weighted signal within the median nerve (arrow). A slightly increased cross sectional area of the nerve is noted but the nerve architecture is preserved, consistent with early or mild inflammation. (Click to enlarge figure)
As with the symptoms of carpal tunnel syndrome, MRI findings in the syndrome may vary with wrist position: flexion or extension of the wrist during the scan can alter the visualization of the median nerve from marked enhancement to complete lack of enhancement, presumably because of mechanical obstruction of blood flow to the nerve. These actions are associated with exacerbation of clinical symptoms.
Figure 5. Carpal tunnel syndrome. Fast spin-echo T2-weighted MRI illustrates more pronounced increased signal within the median nerve (arrow). Note the small amount of fluid within the carpal tunnel, a secondary sign of inflammation. Slightly less optimal fat saturation is noted than on other images, which is a common occurrence. (Click to enlarge figure)
Figure 6. Carpal tunnel syndrome. Axial fast spin-echo T2-weighted MRI with greater increase in signal and loss of definition within the nerve (arrow). Inflammatory change is noted within the carpal tunnel, adjacent to the flexor digitorum superficialis tendons. The appearance is consistent with pronounced inflammatory change within the carpal tunnel. (Click to enlarge figure)
Attempted surgical therapy for carpal tunnel syndrome may result in incomplete release of the flexor retinaculum. This can be detected by a residual increase in T2 signal of the median nerve within the carpal tunnel and by direct visualization of the still-connected fibers of the retinaculum. Transverse carpal ligament release from the hook of the hamate can cause the contents of the carpal canal and/or the flexor tendons to demonstrate a volar convexity caused by the loss of the normal roof support of the flexor retinaculum. In addition to incomplete release of the flexor retinaculum, postoperative MRI changes in failed carpal tunnel surgery include excessive fat within the carpal tunnel, neuromas, scarring, and persistent neuritis. A normal postoperative finding is widening of the fat stripe posterior to the flexor digitorum profundus tendons. MRI studies following carpal tunnel release may demonstrate an increase in carpal tunnel volume of up to 24%, often accompanied by a change in shape from oval to circular, resulting in increased anteroposterior and mediolateral diameters.
In patients who have clinically diagnosed carpal tunnel syndrome without symptoms or signs to suggest other disorders that can mimic carpal tunnel syndrome, it remains controversial as to whether performing nerve conduction studies is necessary or cost-effective. Even less evidence exists regarding the cost-effectiveness of imaging for carpal tunnel syndrome. MR imaging reliably depicts normal carpal tunnel anatomy, including the median and ulnar nerves and their intraneural fascicular structure. It can also identify pathologic nerve compression and mass lesions, such as ganglion cysts, which compress nerves. Currently, MR imaging is probably most commonly used to image patients who have ambiguous electrodiagnostic studies and clinical examinations. MR diffusion-weighted imaging of peripheral nerves might prove to be the most sensitive imaging sequence for the detection of early nerve dysfunction.
Electrodiagnostic studies are likely to remain the pivotal diagnostic examination in patients with suspected carpal tunnel syndrome for the foreseeable future. With advances in imaging software and hardware, however, high-resolution MR imaging of peripheral nerves will become faster, cheaper, and likely more accurate, possibly paving the way for an expanded role in the diagnosis of this common syndrome.
1. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.1a January 2010 [Click to have a look at the home page]
January 28, 2010 — Radiological quiz
Radiological quiz. What is your diagnosis
February 7, 2010 — This section focuses on data pertaining to generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, and posttraumatic stress disorder (PTSD).
Volumetric MRI has been used to show that adolescents who have generalized anxiety disorder have larger white matter and gray matter volumes in the superior temporal gyrus. [1] A right greater than left asymmetry also was noted in this structure and the percent of asymmetry correlated significantly with child report ratings on the Screen for Child Anxiety Related Emotional Disorders scale. This finding is suggestive of structural changes developing early on in the disease process. It remains to be seen whether or not they occur pre-morbidly.
Functional MRI has been used to evaluate intolerance to uncertainty, a major component of generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder. Intolerance to uncertainty correlates positively with bilateral activation of the insula. [2] It may be that increased affective response to situations with uncertain outcomes with corresponding activation of the insula is a trait marker for certain anxiety disorders.
In this area, the data are approaching greater clinical usefulness in that prediction of response to treatment has been demonstrated. In adults who had generalized anxiety disorder, response to venlafaxine was predicted by greater pretreatment reactivity to fearful faces in the rostral anterior cingulate cortex and lesser reactivity in the amygdala as measured by functional MRI. [3] In children and adolescents who had generalized anxiety disorder, this modality was used to predict response not only to medication but also to cognitive behavioral therapy. [4] In this group there was a significant negative association between degree of left amygdala activation and measures of post-treatment symptom improvement.
Disordered caudate nuclear metabolism has long been implicated in the pathophysiology of obsessive-compulsive disorder. [5] In general, alterations of frontostriatal circuitry have been found in various studies. It has been suggested that discordant findings may be the result of different subtypes of the disorder (hoarding, germ phobia, and so forth) with different neurobiologic underpinnings.
Voxel-based morphometry has been used to show significantly lower gray matter density in pediatric obsessive-compulsive disorder patients compared with healthy control subjects in the left anterior cingulate cortex and bilateral medial superior frontal gyrus. [6] When compared with their unaffected siblings, patients displayed significantly greater gray matter volume in the right putamen. In adults, this technique has demonstrated that the dorsal cortical regions of healthy control subjects have significantly greater gray matter volumes than that of patients who have obsessive-compulsive disorder and that in the midbrain bilaterally this relationship is reversed. [7] Furthermore, greater total obsessive-compulsive symptoms were highly significantly related to larger gray matter volumes in the bilateral midbrain.
Response to treatment has been another fruitful area of investigation in obsessive-compulsive disorder. Recently, F18-flourodeoxyglucose (FDG)–positron emission tomography (PET) was used to demonstrate efficacy after only 4 weeks of intensive individual cognitive behavioral therapy. [8] Patients showed significant bilateral decreases in normalized thalamic metabolism and, unexpectedly, an increase in right dorsal anterior cingulate cortex activity that correlated strongly with degree of symptom improvement. It has been postulated that response to intensive cognitive-behavioral therapy may require activation of the dorsal anterior cingulate cortex because of its role in reassessment and suppression of negative emotions.
PTSD has proved another fruitful area in the neuroimaging literature. Several factors may have a bearing on the outcomes, including the type of trauma (eg, physical, sexual, or psychologic), the brain’s maturational stage at the time of the trauma, and the possibility of predisposing vulnerability. Over the past decade, consensus has arisen regarding the role of the amygdala, medial prefrontal cortex, and hippocampus in PTSD. [9] Specifically, amygdala responsivity is positively associated with symptom severity whereas that of the medial prefrontal cortex is inversely associated with the same. The hippocampus in PTSD has been shown to possess decreased volumes and deficiencies in neural and functional integrity.
Recent structural imaging has shown that children who have maltreatment-related PTSD had significantly smaller cerebellar volumes compared with healthy control subjects. [10] Furthermore, cerebellar volumes negatively correlated to the duration of trauma and positively correlated with age of onset of trauma. This adds to the consensus regarding the cerebellums importance in cognitive and emotional development.
Another pediatric study has yielded insights into the complex interplay of stress and developmental damage to the brain. Baseline cortisol levels and PTSD symptoms predicted hippocampal reduction in 15 children over an ensuing 12- to 18-month interval. [1] This is some of the earliest human evidence confirming preclinical data that the glucocorticoids secreted during stress can be neurotoxic to the hippocampus.
A unique group of Vietnam War veterans has afforded the opportunity to assess whether or not the characteristic findings of PTSD reflect the underlying cause or a secondary effect of the disorder. Veterans who had suffered brain injury and emotionally traumatic events exhibited a reduced occurrence of PTSD if they had damage to the ventromedial prefrontal cortex or the anterior temporal area that included the amygdala. [12] This suggests that these two structures are critically involved in the pathogenesis of PTSD.
The interaction of PTSD with other pathologic states also has been addressed. Blood oxygenation level–dependent functional MRI has been used to show reduced pain sensitivity in male veterans suffering from PTSD. [13] Compared to veterans matched for age and region of deployment, patients revealed increased activation in the left hippocampus and decreased activation in the ventrolateral prefrontal cortex bilaterally and in the right amygdala in response to nociception. The patients also rated fixed-temperature noxious conditions as less painful than did control subjects.
Reflecting on the anxiety disorders in general, it has been suggested that fear is a major component and that the amygdala is critical for the acquisition and expression of that emotion. It is hypothesized, however, that it is activity in the prefrontal cortex that controls what individuals who have an anxiety disorder ultimately experience. [14] PTSD, panic disorder, and the phobias—those disorders involving intense fear—seem characterized by underactivity in the prefrontal cortex, thereby disinhibiting the amygdala. Conversely, disorders involving worry and rumination—generalized anxiety disorder and obsessive-compulsive disorder—seem characterized by overactivity of the prefrontal cortex.
