To study the indirect neurological complications in

oncological patients.

Poster No.: C-1918

Congress: ECR 2019
Type: Educational Exhibit
Authors: 1 1 1
B. Raghavan , R. PRASAD , M. Logudas , R. H. ARAFATH , P.
2

1 1 3 1
Gopalakrishnan , R. dommaraju , J. Govindaraj ; Chennai/IN,
2 3
CHENNAI, TAMILNADU/IN, Chennai, TN/IN
Keywords: Cancer, Radiation effects, Complications, MR, CT, Oncology, CNS
DOI: 10.26044/ecr2019/C-1918

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Page 1 of 20
Learning objectives

Objective of our study is to study the indirect neurological complications of cancer, and
its treatment in patients who presented with neurological symptoms.

Page 2 of 20
Background

Cancer often affects the nervous system and may result in significant neurologic morbidity
and mortality.

These effects may be

Direct-with direct cancer involvement of the brain or spine,

Indirect as in paraneoplastic neurologic syndromes.

Direct complications:

1.Parenchymal metastases to the brain from systemic malignancies commonly originates

from lung, breast, and melanoma. Brain metastases are rare in prostate cancer [1]

2. Leptomeningeal Metastases is seen mostly in small cell lung cancer [3], breast cancer
[4], and melanoma [5] ,non-Hodgkin's lymphoma (NHL) [6] and acute nonlymphocytic
leukemia [7]The largest autopsy series to date indicates that 8% of patients with cancer
have leptomeningeal seeding at autopsy [2].

Indirect Complications of Cancer and cancer treatment:

1. Paraneoplastic Syndromes:

Neurologic paraneoplastic syndromes (NPNS) are disorders caused by cancer without

direct infiltration, metastases, or compression of the CNS or PNS structure involved as
determined by clinical presentation. The mechanism is autoimmune and recognition of
these syndromes is very important as it may lead to an early cancer diagnosis.

2. Cerebrovascular Complications of Cancer and cancer treatment:

Ischemic Stroke-Cancer patients are at risk for cerebrovascular complications for three
reasons:

i) Cancer and its treatment result in disorders of coagulation;

ii) Cancer may directly affect blood vessels; and

iii) Infections in individuals who are immunocompromised may result in secondary stroke
[8].

3. Posterior reversible encephalopathy syndrome (PRES):

Page 3 of 20
PRES is a well-described clinicoradiographic entity of encephalopathy, seizures, and
other neurologic symptoms, with characteristic neuroimaging demonstrating lesions with
posterior and white matter predominance [9-13]

Case reports have implicated various chemotherapy agents and other drugs commonly
used in patients with cancer [10,14,17-21]. As molecularly targeted therapy becomes
more prevalent in oncology, newer agents may become important contributors to this
condition [22-30].

4. Nervous System Complications from Radiation Therapy:

The central and peripheral nervous system may be affected by radiation therapy. In the
brain and spinal cord this is believed to be caused by a combination of vascular damage
and damage to glia, mainly oligodendrocytes. The timing from completion of radiation (6
months-12months post radiation) is crucial to the diagnosis of radiation necrosis. as this
condiation is reversible [29].

5.Chemotherapy agents can result in toxicity to the nervous system.

Table showing chemotherapy agents and their complication Fig.1.

Page 4 of 20
Images for this section:

Fig. 1: Table showing chemotherapy agents and their complication.Modified from

Neurologic Complications of Cancer and its Treatment by Pierre Giglio and Mark R.
Gilbert[35], and[32-34].

© Neurologic Complications of Cancer and its Treatment Pierre GiglioDepartment of

Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB
306B, Charleston, SC 29425, USA giglio@musc.edu and Mark R. GilbertDepartment of
Neuro-oncology, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston,
TX 77030, USA.

Page 5 of 20
Findings and procedure details

In our prospective observational study, from April 2017 till date. Out of 351 patients who
were having a known extracalvarial malignancy presented in our hospital with new onset
neurological symptoms and subsequently underwent neuroimaging using computed
tomography or magnetic resonance imaging. Of these 301 patient were excluded as they
had normal neuroimaging findings(178),old ischemic changes (44), direct neurological
complications (79). The remaining 50 patient having indirect neurological complications
were included in the study.

These patients detailed past medical history were reviewed including the primary
malignancy, the treatment modality/modalities the patient had undergone or were
undergoing. The presenting complains as well as the old neuroimaging (If available) were
also reviewed.

The distribution of the various indirect complications of these patient is given in Fig.2

Following are the representing cases of the complications which we encountered.

1. POSTERIOR REVESIBLE ENCEPHALOPATHY SYNDROME:Fig.3

2. CENTRAL PONTINE MYELINOLYSIS:Fig.4

3. VENOUS SINUS THROMBOSIS:Fig.5

4. ACUTE INFARCT:Fig.6

5. RADIATION NECROSIS:Fig.7

6. INTRAPARENCHYMA HEMORRHAGE:Fig.8

7.POSTERIOR REVESIBLE ENCEPHALOPATHY SYNDROME:Fig.9

Page 6 of 20
In our study Posterior reversible encephalopathy was the most common indirect
neurological complication in our patients and is seen in 52% of the patient ,which carries
a good prognosis with conservative management.

Acute infarct in the neuroparenchyma was the second most common complication seen
in 18% of the patients which carried a mixed prognosis with most patient improving on
consevative management.

Acute intraparenchymal hemorrhage was the third most common complications seen in
14% of cases which carried a poor prognosis with high mortality among the patients.

Venous sinus thrombosis was also a common complication in our group seen in 12% of
patients and usually carried good response if there was no associated infarction.

Post radiation necrosis was also observed and was a subacute to late complication and
2% cases and was managed conservatively and the patient is improved.

Post-op complications included electrolyte imbalance which lead to the cental pontine
myelinolysis was seen in 2% cases the patient managed conservatively and condition
improved.

92% of our patients having indirect neurolgical complication were on chemotherapy and
PRES was the commonest complication. Fig.10

Page 7 of 20
Images for this section:

Fig. 2: Pie distribution chart of the indirect complications in our study patients

© RADIOLOGY, APOLLO SPECIALITY HOSPITAL - Chennai/IN

Page 8 of 20
Fig. 3: A 72 year old female patient of carcinoma endometrium who underwent radical
hysterectomy in feb 2018, PET CT dated 15th june showed normal neuroparenchyma
with omental disease.On 25thjune patient presented with drowisness. A & B ARE PET
CT image which in done on 15th june and shows normal neuroparenchyma. C & D are CT
brain images which was done on 25th june and which showed asymmetrical hypodensity
in left posterior parietal and right occipital cortices-consistent with finding of Posterior
reversible encephalopathy.

© RADIOLOGY, APOLLO SPECIALITY HOSPITAL - Chennai/IN

Page 9 of 20
Fig. 4: 55 year old male who is a known case of carcinoma rectum status post surgery in
2015 and chemotherapy - XELOX regimen,recently developed hydroureteronephrosis-
likely due to ureteric stricture/ adhesion band narrowing the ureters.Presented to ER with
altered sensorium.Patient had hyponatremia. MRI brain showed area of hyperintensity
in pons in T2WI and FLAIR images-suggesting diagnosis of central pontinemyelinolysis

© RADIOLOGY, APOLLO SPECIALITY HOSPITAL - Chennai/IN

Page 10 of 20
Fig. 5: 54year old male patient of carcinoma hypopharynx who underwent total
laryngectomy with partial hypopharyngectomy with selective neck dissection on 4th
october.Presented to ER on 14 October with complains of giddiness followed by
left sided weakness MR Venogram showing thrombosis of the right transverse and
sigmoid sinuses.There was no restriction on diffusion images suggesting venous sinus
thrombosis without infarct.

© RADIOLOGY, APOLLO SPECIALITY HOSPITAL - Chennai/IN

Page 11 of 20
Fig. 6: 49 years old patient of bilateral carcinoma ovary with metastatic pelvic and
right inguinal nodes post primary cytoreductive surgery on 27/06/17. Patient started on
chemotherapy mitomax and carboplatin.On 14-7-17 the patient presented to ER with right
sided sudden onset weakness. Diffusion weighted images showing restricted diffusion
in the left high parietal and occipital cortices with non territorial location. on FFE image
linear blooming seen in the left occipital cortex-acute venous infarct due to cortical vein
thrombosis.

© RADIOLOGY, APOLLO SPECIALITY HOSPITAL - Chennai/IN

Page 12 of 20
Fig. 7: A 62 year old female who had right lateral sphenoid wing atypical
meningioma-WHO grade II underwent gross total resection of the lesion followed by
radiotherapy.Presented to ER 3 months later with complains of drowsiness and altered
sensorium. MRI brain showed a heterointense lesion in right centrum semiovale which
shows diffusion restriction and frond-like peripheral enhancement.On MRS it shows mildy
elevated choline peak with reduced NAA peak. Cho/cr-2.4 and cho/NAA-2.0.-suggeting
the diagnosis of radiation necrosis.

© RADIOLOGY, APOLLO SPECIALITY HOSPITAL - Chennai/IN

Page 13 of 20
Fig. 8: A 66 Year old male carcinoma prostate patient with skeletal metastases, the PET
CT done on 26th july showed normal neuroparenchyma, the following day the patient
presented to ER in unconcious state. Image A & B PET CT images which was done on
26/7/18 showing normal neuroparenchyma, C & D are the CT image taken on 27/7/18
which shows acute intraparenchyma hemorrhage in left frontal cortex with acute subdural
hemorrhage in left fronto-parietal convexity.

© RADIOLOGY, APOLLO SPECIALITY HOSPITAL - Chennai/IN

Page 14 of 20
Fig. 9: A 52 year old female patient of ALL, Who received 3 cycles of Hyper
CVAD + Dasatinib and 8 Cycle lumbar puncture and intrathecal prophylaxsis
(Four with Methotrexate and four with Cytarabine).Came to ER with complaints of
altered sensorium. MRI brain shows Symmetrical T2 and FLAIR hyperintensities in
both the posterior parietal and occipital cortices-consistent with Posterior reversible
encephalopathy.

© RADIOLOGY, APOLLO SPECIALITY HOSPITAL - Chennai/IN

Page 15 of 20
Fig. 10: Bar distribution of the various indirect complications,with number of patients who
were on chemotherapy and who were not on chemotherapy in each respective group.

© RADIOLOGY, APOLLO SPECIALITY HOSPITAL - Chennai/IN

Page 16 of 20
Conclusion

In our study 92 % of the patient developing indirect neurological complication were on

chemotherapy .Fig 10.

The most common indirect neurological complication was PRES (posterior reversible
encephalopathy) in our series, and was seen maximum in patients who were on
chemotherapy and, Dasatinib was the single most common offending agent. Patients
with posterior reversible encephalopathy do well with conservative management.

At the other end of spectrum acute intraparenchymal hemorrhage which is also seen
in patient who were on chemotherapy carries a poor prognosis even with agressive
treatment.

Radiation necrosis mimics a recurrent disease however typical MRI frond like appearance
and MRS finding of mildly increased choline peak with reduced N-acetylaspartate
clinches the diagnosis.

Identifying the indirect neurological complications in cancer patients can help in modifying
the treatment and can reduce treatment associated morbidity and mortality there by
reducing the overall healthcare cost.

Page 17 of 20
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35. Neurologic Complications of Cancer and its Treatment Pierre GiglioDepartment of

Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB
306B, Charleston, SC 29425, USA giglio@musc.edu and Mark R. GilbertDepartment of
Neuro-oncology, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston,
TX 77030, USA.

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