Differential Diagnosis in Neurology

1.2. Venous Strokes

Venous strokes should be suspected in the setting of the last trimester of pregnancy and the first month of the perineurium, any prothrombotic state and dehydration. Clinically, there is a depressed mental status early in the course of the process as well as a step wise and progressive onset rather than an apoplectic initial event, which characterizes embolus, hemorrhage and ischemic stroke. Repeated seizures and vomiting are common associated with severe headache. Papilledema is more common than with ischemic or hemorrhagic events. The sinuses are commonly occluded. Lateral sinus involvement should be suspected with mastoid pain that may radiate to the sternocleidomastoid muscle associated with Vth and VIth nerve involvement. The temporal lobe and cerebellum may be involved concomitantly. The sagittal sinus frequently presents with focal seizures of the leg or bilateral signs and symptoms. Severe headache, papilledema and rapid loss of consciousness strengthen the diagnosis. Cavernous sinus involvement is frequently heralded by periorbital headache, fever, stiff neck. There is progressive orbital and retinal congestion culminating in paresis of III, IV, VI, V. Often there is complete ophthalmoplegia and frequent spread to the contralateral eye.

Occlusion of the internal cerebral veins, veins of Galen and straight sinus present in stupor or coma. They often have had a severe headache and hemiparesis prior to depression of mental status.

Cortical cerebral venous occlusion presents with focal neurological signs, seizures at presentation, headache but minimal depression of consciousness.

Cerebellar venous occlusions often pursue a pseudotumoral course with brainstem compression.

MRI evaluation that demonstrates a delta sign at the confluences of sinuses, bilateral thalamic and basal ganglia hemorrhage, small compressed ventricles and vascular lesions out of a typical arterial distribution suggest venous stroke and sinus occlusion. The following is a detailed discussion of the major differential points of venous stroke and specific sinus occlusion.

General Features of Venous Strokes

Specific territories of venous drainage

• Superior sagittal sinus (SSS) and its veins
  • Drain a major part of the cerebral hemispheres
• Inferior sagittal sinus, straight sinus and tributaries drain
  • Deep white matter of the cerebral hemispheres
  • Basal ganglia
• At the torcular of Herophilus (confluens of sinuses)
  • SSS is continuous with the right lateral sinus
  • Straight sinus continuous with the left
• Lateral sinus (two segments)
  • Transverse (attached to the border of the tentorium)
  • Sigmoid (attached to the inner aspect of the mastoid bone)
• Cavernous sinus
  • Drains periorbital and facial territories
  • Joins the internal jugular vein and transverse sinus through the petrosal sinus
  • Drains Sylvian fissure through the sphenoparietal sinus

Pattern of Pathology

• Superior sagittal sinus thrombosis with cortical vein thrombosis
  • Involves the superficial cerebral hemispheres
• Thrombosis of the straight sinus involves the basal ganglia
• Isolated cortical vein thrombosis is rare
• Usual pathology: venous thrombosis with or without cerebral infarction, basal ganglia or thalamic hemorrhage
• Venous obstruction causes:
  • Cerebral edema
  • Infarction or hemorrhagic infarction of the cortex
  • Petechial hemorrhage
  • Superior sagittal sinus thrombosis may cause:
    • Bilateral basal ganglia hemorrhage
    • Unilateral or bilateral thalamic hemorrhage
  • Hemorrhagic infarction circumscribed or wide spread that may involve cortical and deep structures
  • Multiple or single intracerebral hemorrhage

Venous Sinus Thrombosis

General Signs and Symptoms

• General Features:
  • Seizures with severe headaches
  • Depressed mental status early in the course of illness with papilledema (40%)
  • Stepwise and progressive onset
  • Vomiting common
  • Repeated seizures
  • Hemiparesis commonest focal deficit
  • Hemisensory symptoms approximately 10%
  • Neurologic signs are cumulative
  • Alternating or ascending hemiparesis is rare
  • Bloody cerebral spinal fluid
• Causes of venous thrombosis
• Clotting disorders:
  • Antithrombin III
  • Protein C and S deficiency
  • Factor V Leiden mutation
  • Prothrombin gene mutation
  • SLE anticoagulant
  • Activated Protein C resistance
  • Methylene tetrahydrofolate reductase deficiency
  • Anticardiolipin antibody
  • Increased factor VIII
  • Oral contraceptives
  • Ulcerative colitis
  • Regional enteritis
  • Polycythemia vera
  • Hemolytic anemia
  • Pregnancy and the puerperium
  • Leukemia
  • Paroxysmal nocturnal hemo globulinuria (decreased membrane glyco protein)
  • Carcinoma (thrombin like material)
  • Idiopathic thrombocytosis
  • Nephrotic syndrome
  • Ménétriér's syndrome (protein losing enteropathy)
  • Androgen therapy
  • Asparaginase therapy (blocks antithrombin III)
  • Cryofibrinogenemia
  • Disseminated intravascular dissemination
  • Behçet's disease
• Changes in the Venous Sinus Wall
  • Metastatic disease (invasion)
    • lung; breast, choriocarcinoma, prostate
  • Lymphoma (invasion)
  • Non-Hodgkin's lymphoma
  • Behçet's disease
  • Arteriovenous malformation
  • Sarcoidosis
  • Leukemia (invasion of wall)
  • Meningitis
  • Chronic otitis media
  • Wegener's granulomatosis
  • Aspergillosis
  • Mastoiditis (lateral sinus)
• Blood Flow, Rheology, Systemic Causes of Venous Occlusion
  • Congestive heart failure
  • Cachexia and marasmus
  • Trauma
  • Cerebral artery thrombosis
  • Chronic obstructive airway disease
  • Trichinosis
  • Transvenous pacemaker placement
  • Dehydration
  • Hyperpyrexia (release of thromboplastin from platelets)
  • Congential heart disease
  • Budd–Chiari syndrome
  • Diabetes mellitus
  • Vasculitis
  • Homocystinuria
  • SS disease

Clinical Signs and Symptoms of Specific Sinus Thrombosis

• General epidemiology
  • The SSS is the most commonly involved
    • Involved alone approximately 30–40% of the time
  • Unilateral lateral sinus thrombosis, 10–15% of patients
• Rarer involvement
  • Deep venous system
  • Cerebellar veins
  • Isolated cortical veins

Lateral Sinus Thrombosis

• Etiology
  • Coagulopathy and systemic illness
  • Spread of infection from middle ear and mastoid
    • Infection spreads through emissary veins
    • Spread of infection from the lateral sinus through jugular veins
  • Infection from central venous lines
• Lateral sinus thrombosis from otic causes:
  • Draining ears and perforated ear drums
  • Pain occurs:
    • Mastoid area
    • Sternocleidomastoid muscle
    • Headaches in frontotemporal and occipital areas
  • Vertigo, nausea and vomiting
  • Diplopia VIth nerve involvement (Dorello's canal at the petrous apex under the petroclinoid ligament)
  • Vth nerve involvement (Meckel's cave)
  • Vth/VIth nerve involvement (Gradenigo's Syndrome)
    • Nerves are affected at the petrous apex
    • Requires pneumatized temporal bone
  • Lethargy (increased ICP)
  • Temporal lobe and cerebellum involved concomitantly
• Approximately 2/3 of patients have involvement of more than one sinus
• SSS involved more commonly than expected during the puerperium
• Septic processes frequently involve the cavernous and lateral sinus

Sagittal Sinus Thrombosis

• Etiology:
  • Puerperium
  • Parasagittal meningioma
  • Carcinomatosis of the meninges
    • Breast and prostate carcinoma
  • Head trauma
  • Behçet's disease
  • Prothrombotic states
  • Paranasal sinus involvement
• Clinical signs and symptoms
  • Depends on concomitant involvement of cortical veins
    • Focal motor or sensory deficits
    • Seizures (leg > arm)
    • Bilateral signs and symptoms
    • May have transient signs and symptoms
  • Pseudotumor cerebri if SSS is involved alone:
    • Severe headache
    • Papilledema
    • VIth nerve palsy
    • Decreased level of consciousness
    • Edema and hemorrhage of the medial dorsal cerebral hemisphere
• Temporal lobe involvement
  • Posterior aphasia
  • Superior quadrantanopia
  • Agitation
• Cerebellar involvement
  • Gait ataxia
  • Ipsilateral rotary nystagmus
• Spread of thrombus:
  • Into jugular vein (if an axillary or jugular line is infected the spread is to the lateral sinus)
  • Adjacent dural sinuses
  • Rare concomitant pulmonary emboli
• Imaging studies:
  • Lytic lesions, opacification of mastoid air cells, eburnation and bone sclerosis
  • Secondary cholesteatoma

Cavernous Sinus Thrombosis

• Etiology
  • Infection of veins draining the medial face, orbit, nose and nasal sinuses
  • Infectious etiologies
    • Staphylococcus aureus
    • Pneumococci
    • Streptococci
    • Gram negative bacteria
    • Mucormycosis
    • Aspergillus
  • Noninfectious etiologies
    • Surgery of sinuses/facial structures
    • Prothrombotic states
    • Thrombosis of dural A-V fistula
• Clinical Features:
  • Fever; often with stiff neck
  • Headache (particularly periorbital)
  • Facial pain
  • Conjunctival edema and erythema
  • Orbital and retinal congestion
  • Dysfunction of:
    • III, IV, V nerves
    • V1 and occasionally V2
    • Complete ophthalmoplegia
    • Occlusion of ophthalmic artery (blindness)
    • Bilateral eye findings
    • Involvement of ICA with hemiparesis (rare)
    • Cavernous sinus thrombosis with spread to superior petrosal sinus
      • Vth nerve is involved
  • Noninfectious etiologies
    • Indolent course
    • Proptosis
    • Conjunctival edema
    • No or minimal occulomotor involvement
• Cavernous sinus anatomy
  • Anterior and posterior intercavernous sinus (connects the two sides)
  • Inferior petrosal sinus drains into the sigmoid sinus
  • Superior petrosal sinus drains into the transverse or sigmoid sinus

Internal Cerebral Veins: Vein of Galen and Straight Sinus

• Deep system drains:
  • Thalamus
  • Basal ganglia
  • Midbrain
  • Geniculate bodies
  • Cerebellum
• Etiology:
  • Dehydration
  • Sickle cell disease
  • Infection
  • Ulcerative colitis
  • Oral contraceptives
• Internal cerebral vein and vein of Galen occlusion:
  • Clinical features
    • Patients present stuporous or in coma
    • Severe headache may precede decreased level of consciousness
    • Hemiparesis
  • Thalamic and basal ganglemic hemorrhage
    • Coma
    • Decerebrate posture
    • Vertical gaze palsy
    • Apathy and abulia in some patients as a presenting sign

Jugular Vein Thrombosis

• Clinical features:
  • Headache
  • Fever
  • Vomiting
  • Involvement of IX, X, XI cranial nerves

Cortical Cerebral Venous Thrombosis

• Clinical features:
  • Seizures at presentation
  • Focal neurological signs
    • Aphasia
    • Hemiparesis
  • Headache
  • Less commonly a decreased level of consciousness
• MRI evaluation:
  • Brain edema with hemorrhage
  • Pial surface of the hemisphere is involved

Cerebellar Venous Occlusion

• Clinical features:
  • Severe headache
  • Incoordination
  • Cranial nerve palsies
  • Pseudotumoral course with brainstem compression
• Clinical Features of Venous Sinus Compression from Tumor Metastasis Usual Tumors:
  • Ewing's sarcoma (occipital region of skull)
  • Plasmacytoma
  • Metastatic lung cancer
  • Neuroblastoma
  • Choriocarcinoma
  • Metastatic breast carcinoma

Differential rests between mass beneath the inner table of skull versus tumor invasion of the dura and sinus. Isolated dural sinus thrombosis may be benign.

• Diagnostic Features of Venous Occlusive Disease:
  • Specific circumstances as noted
  • Headaches is often the presenting symptom
  • Seizure and lethargy more common than in arterial disease
  • Increased intracranial pressure in the absence of focal deficits
  • Slower and more indolent progression than arterial disease
• Imaging evaluation:
  • CT:
    • Evidence of sinus and middle ear disease
    • Cord sign
      • Cerebral vein imaged as high density linear, thin tubular structure
    • Delta sign at the confluens of sinuses
      • Hyperdense triangular mass within the sinus on contrast CT; which does not enhance
    • Bilateral thalamic and basal ganglia hemorrhage
    • Small compressed ventricles
    • Lesions out of a typical arterial distribution
  • Contrast enhanced CT:
    • Dilated cortical and medullary veins
    • Gyral enhancement
  • Deep Venous Occlusion demonstration by CT
    • Bilateral hypodensity of thalamus and basal ganglia
    • Edema and compression of the IIIrd ventricle
    • Retention of contrast in thalamostriate veins, basilar vein of Rosenthal, non- opacification of vein of Galen
  • MRI/MRV:
    • May directly image the occluded venous sinus
    • Demonstrates collaterals
  • Arteriography
    • Delineates all venous and arterial structures
      • Now necessary as angioplasty and intravenous thrombotics may be options
      • Better visualization of congenital variants
    • Multifocal and bilateral
    • Seizures and increased intracranial pressure
    • Cortical surface causes focal leg seizure (superior sagittal sinus) or arm (cortical vein)